85 results on '"D. Le-Nguyen"'
Search Results
2. Regional personality assessment through social media language
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Salvatore Giorgi, Lyle H. Ungar, Khoa D. Le Nguyen, Margaret L. Kern, Michal Kosinski, Gregory Park, David B. Yaden, Martin E. P. Seligman, Johannes C. Eichstaedt, and H. Andrew Schwartz
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Agreeableness ,Extraversion and introversion ,Social Psychology ,media_common.quotation_subject ,Life satisfaction ,Conscientiousness ,Personality Assessment ,Article ,Extraversion, Psychological ,Openness to experience ,Humans ,Personality ,Big Five personality traits ,Personality Assessment Inventory ,Psychology ,Social Media ,Social psychology ,Language ,media_common - Abstract
OBJECTIVE: We explore the personality of counties as assessed through linguistic patterns on social media. Such studies were previously limited by the cost and feasibility of large-scale surveys; however, language-based computational models applied to large social media datasets now allow for large-scale personality assessment. METHOD: We applied a language-based assessment of the five factor model of personality to 6,064,267 U.S. Twitter users. We aggregated the Twitter-based personality scores to 2,041 counties and compared to political, economic, social, and health outcomes measured through surveys and by government agencies. RESULTS: There was significant personality variation across counties. Openness to experience was higher on the coasts, conscientiousness was uniformly spread, extraversion was higher in southern states, agreeableness was higher in western states, and emotional stability was highest in the south. Across 13 outcomes, language-based personality estimates replicated patterns that have been observed in individual-level and geographic studies. This includes higher Republican vote share in less agreeable counties and increased life satisfaction in more conscientious counties. CONCLUSIONS: Results suggest that regions vary in their personality and that these differences can be studied through computational linguistic analysis of social media. Furthermore, these methods may be used to explore other psychological constructs across geographies.
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- 2021
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3. The goods in everyday love: Positivity resonance builds prosociality
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Jieni Zhou, Taylor N. West, Barbara L. Fredrickson, Khoa D. Le Nguyen, and Michael Prinzing
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Adult ,Social connectedness ,Flourishing ,media_common.quotation_subject ,Emotions ,PsycINFO ,Love ,Developmental psychology ,Nonverbal communication ,Corollary ,Intervention (counseling) ,Perception ,Humans ,Psychology ,Practical implications ,General Psychology ,media_common - Abstract
The positivity resonance theory of coexperienced positive affect (Fredrickson, 2016) identifies the emotion of love as a collective state. This state, termed positive resonance, is defined by the presence of three key features: shared positive affect, caring nonverbal synchrony, and biological synchrony. The current study examined whether a modest behavioral intervention focused on increasing social connectedness could increase study participants' perceptions of day-to-day positivity resonance with corollary impacts on their tendencies for prosociality and self-centeredness. Adults (N = 416, M age = 33.8) were randomized to one of four study conditions: either of two variants of the social connectedness intervention or either of two control groups. Positivity resonance, prosociality, and self-centeredness were measured nightly for 35 consecutive days. Dynamic multilevel factor models of nightly reports showed significant growth in positivity resonance, relative to a passive control group, for the two intervention groups and higher mean levels of prosociality for one of them. In addition, significant dose-response relations were evident (both between persons and within persons), linking positivity resonance to both prosociality and self-centeredness. The within-persons effect for prosociality (but not self-centeredness) was significantly stronger for those randomized to the intervention groups, relative to both passive and active control groups. Taken together, findings suggest that the affective quality of people's day-to-day social encounters may have implications for community flourishing. Discussion centers on theoretical and practical implications as well as directions for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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- 2021
4. Staying ‘in sync’ with others during COVID-19: Perceived positivity resonance mediates cross-sectional and longitudinal links between trait resilience and mental health
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Michael M. Prinzing, Jieni Zhou, Taylor N. West, Khoa D. Le Nguyen, Jenna L. Wells, and Barbara L. Fredrickson
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media_common.quotation_subject ,05 social sciences ,050109 social psychology ,Affective science ,Broaden-and-build ,Mental health ,050105 experimental psychology ,Social relation ,mental disorders ,Well-being ,Trait ,0501 psychology and cognitive sciences ,Positive psychology ,Psychological resilience ,Psychology ,psychological phenomena and processes ,General Psychology ,Clinical psychology ,media_common - Abstract
Shared positive emotions involving caring and synchrony – termed ‘positivity resonance’ – are associated with mental health. We hypothesized that, during the COVID-19 pandemic, individual differenc...
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- 2020
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5. Well-Being Correlates of Perceived Positivity Resonance: Evidence From Trait and Episode-Level Assessments
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Barbara L. Fredrickson, Khoa D. Le Nguyen, Brett C Major, and Kristjen B. Lundberg
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Adult ,Male ,Social Psychology ,Emotions ,050109 social psychology ,Article ,050105 experimental psychology ,mental disorders ,medicine ,Humans ,Interpersonal Relations ,0501 psychology and cognitive sciences ,Social Identification ,Depression ,Loneliness ,Flourishing ,05 social sciences ,Construct validity ,Mental health ,Social relation ,Affect ,Mental Health ,Social Perception ,Well-being ,Trait ,Female ,Perception ,Positive psychology ,medicine.symptom ,Psychology ,Social psychology ,psychological phenomena and processes ,Clinical psychology - Abstract
Positivity resonance is a type of interpersonal connection characterized by shared positivity, mutual care and concern, and behavioral and biological synchrony. Perceived positivity resonance is hypothesized to be associated with well-being. In three studies (N = 175; N = 120; N = 173), perceived positivity resonance was assessed at the trait level (Study 1) or the episode level, using the Day Reconstruction Method (Studies 2 and 3). Primary analyses reveal that perceived positivity resonance is associated with flourishing mental health, depressive symptoms, loneliness, and illness symptoms. These associations largely remain statistically significant when controlling for daily pleasant emotions or social interaction more generally. Ancillary analyses in Studies 2 and 3 support the construct validity of the episode-level assessment of perceived positivity resonance. The overall pattern of results is consistent with Positivity Resonance Theory (Fredrickson, 2016). Discussion centers on avenues for future research and the need for behavioral interventions.
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- 2018
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6. The noetic quality: A multimethod exploratory study
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Laura K. Smith, Khoa D. Le Nguyen, Anneke Buffone, Johannes C. Eichstaedt, Andrew B. Newberg, Margaret L. Kern, Ralph W. Hood, David B. Yaden, H. Andrew Schwartz, Mark R. Waldman, and Nancy Wintering
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Psychotherapist ,Social Psychology ,media_common.quotation_subject ,Exploratory research ,Experimental and Cognitive Psychology ,Clinical Psychology ,Neuropsychology and Physiological Psychology ,Religious experience ,Spirituality ,Quality (business) ,Psychology ,Social psychology ,Mysticism ,media_common - Published
- 2017
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7. Loving-kindness meditation slows biological aging in novices: Evidence from a 12-week randomized controlled trial
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Sumi L. Kim, Jeffrey Brantley, Khoa D. Le Nguyen, Jue Lin, Sharon Salzberg, Mary M. Brantley, Barbara L. Fredrickson, and Sara B. Algoe
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Adult ,Male ,medicine.medical_specialty ,Aging ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Emotions ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Group differences ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Loving kindness meditation ,Meditation ,Biological Psychiatry ,media_common ,Endocrine and Autonomic Systems ,business.industry ,Telomere Homeostasis ,Middle Aged ,Telomere ,030227 psychiatry ,Psychiatry and Mental health ,Mindfulness meditation ,Female ,business ,Cell aging ,Mindfulness ,030217 neurology & neurosurgery - Abstract
Combinations of multiple meditation practices have been shown to reduce the attrition of telomeres, the protective caps of chromosomes ( Carlson et al., 2015 ). Here, we probed the distinct effects on telomere length (TL) of mindfulness meditation (MM) and loving-kindness meditation (LKM). Midlife adults (N = 142) were randomized to be in a waitlist control condition or to learn either MM or LKM in a 6-week workshop. Telomere length was assessed 2 weeks before the start of the workshops and 3 weeks after their termination. After controlling for appropriate demographic covariates and baseline TL, we found TL decreased significantly in the MM group and the control group, but not in the LKM group. There was also significantly less TL attrition in the LKM group than the control group. The MM group showed changes in TL that were intermediate between the LKM and control groups yet not significantly different from either. Self-reported emotions and practice intensity (duration and frequency) did not mediate these observed group differences. This study is the first to disentangle the effects of LKM and MM on TL and suggests that LKM may buffer telomere attrition.
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- 2019
8. The language of ineffability: Linguistic analysis of mystical experiences
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Khoa D. Le Nguyen, Margaret L. Kern, David B. Yaden, Andrew B. Newberg, Nancy Wintering, Johannes C. Eichstaedt, Ralph W. Hood, and H. Andrew Schwartz
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Social Psychology ,Inclusion (disability rights) ,05 social sciences ,Religious studies ,Ineffability ,050109 social psychology ,050105 experimental psychology ,Linguistic analysis ,Religious experience ,Spirituality ,0501 psychology and cognitive sciences ,Psychology ,Social psychology ,Applied Psychology ,Mysticism - Abstract
Mystical experiences are often described as “ineffable,” or beyond language. However, people readily speak about their mystical experiences if asked about them. How do people describe what is supposedly indescribable? In this study, we used quantitative linguistic analyses to interpret the writings of 777 participants (45.5% female, 51.0% male) who recounted their most significant spiritual or religious experience as part of an online survey. High and low scorers on a measure of mystical experiences differed in the language they used to describe their experiences. Participants who have had mystical experiences used language that was more socially and spatially inclusive (e.g., “close,” “we,” “with”) and used fewer overtly religious words (e.g., “prayed,” “Christ,” “church”) than participants without such experiences. Results indicated that people can meaningfully communicate their mystical experiences, and that quantitative language analyses provide a means for understanding aspects of such experiences.
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- 2016
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9. 16/ People in the Zoo
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Susan Clayton and Khoa D. Le Nguyen
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- 2018
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10. Positive Emotions and Well-Being
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Khoa D. Le Nguyen and Barbara L. Fredrickson
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Action (philosophy) ,Cultural context ,Causal effect ,Well-being ,Physical health ,Cognition ,Affect (psychology) ,Psychology ,Social psychology ,Fundamental human needs - Abstract
The ensuing research has revealed that positive emotions serve a wide range of essential human needs. Happier people have better physical health, live longer and are more successful, creative, and socially connected. Emotions are a subclass of affective phenomena. Affect is a neurophysiological state that is subjectively experienced as being pleasant versus unpleasant and being sleepy versus activated. Beyond building psychological resilience, positive emotions may also build behavioral and biological resources that benefit physical health. The effects of positive emotions on well-being may depend on a person's cultural context. Cultures have different conceptions of well-being, and as such, well-being appears to be attained by pursuing diverging goals. Ample evidence has shown that negative emotions narrow attention and cognition, and trigger specific action tendencies. An increasing body of research has supported the broaden-and-build theory by shedding light on the causal effect of positive emotions on well-being via biological and psychological pathways.
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- 2017
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11. Corrigendum to 'Loving-kindness meditation slows biological aging in novices: Evidence from a 12-week randomized controlled trial' [Psychoneuroendocrinology 108 (2019) (October) 20–27]
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Sara B. Algoe, Sumi L. Kim, Barbara L. Fredrickson, Sharon Salzberg, Mary M. Brantley, Jeffrey Brantley, Jue Lin, and Khoa D. Le Nguyen
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Psychiatry and Mental health ,Endocrinology ,Psychotherapist ,Randomized controlled trial ,Endocrine and Autonomic Systems ,law ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Loving kindness meditation ,Psychology ,Biological Psychiatry ,law.invention ,Psychoneuroendocrinology - Published
- 2019
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12. Of Roots and Fruits: A Comparison of Psychedelic and Nonpsychedelic Mystical Experiences
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Johannes C. Eichstaedt, Mary Ellen Smith, Alexander B. Belser, Jonathan Iwry, Nancy Wintering, David B. Yaden, Margaret L. Kern, Ralph W. Hood, Andrew B. Newberg, and Khoa D. Le Nguyen
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Psychotherapist ,Sociology and Political Science ,Social Psychology ,Psychedelic substances ,Existentialism ,030227 psychiatry ,Psilocybin ,03 medical and health sciences ,Philosophy ,0302 clinical medicine ,Religious experience ,Spirituality ,medicine ,Psychology ,Socioeconomic status ,030217 neurology & neurosurgery ,Fear of death ,Mysticism ,medicine.drug - Abstract
Experiences of profound existential or spiritual significance can be triggered reliably through psychopharmacological means using psychedelic substances. However, little is known about the benefits of religious, spiritual, or mystical experiences (RSMEs) prompted by psychedelic substances, as compared with those that occur through other means. In this study, 739 self-selected participants reported the psychological impact of their RSMEs and indicated whether they were induced by a psychedelic substance. Experiences induced by psychedelic substances were rated as more intensely mystical ( d = .75, p < .001), resulted in a reduced fear of death ( d = .21, p < .01), increased sense of purpose ( d = .18, p < .05), and increased spirituality ( d = .28, p < .001) as compared with nonpsychedelically triggered RSMEs. These results remained significant in an expanded model controlling for gender, education, socioeconomic status, and religious affiliation. These findings lend support to the growing consensus that RSMEs induced with psychedelic substances are genuinely mystical and generally positive in outcome.
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- 2017
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13. Solid-phase synthesis, conformational analysis, and biological activity of AVRp elicitor peptides of the fungal tomato pathogen Cladosporium falvum
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J.J.M. Vervoort, H. W. Van den Hooven, P.J.G.M. de Wit, E. Mahe, D. Le-Nguyen, and P. Vossen
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chemistry.chemical_classification ,Stereochemistry ,Chemical structure ,Cystine knot ,Mutant ,Biological activity ,Peptide ,Nuclear magnetic resonance spectroscopy ,Biology ,Biochemistry ,Elicitor ,Endocrinology ,Solid-phase synthesis ,chemistry - Abstract
The race-specific peptide elicitor AVR9 of the fungal pathogen Cladosporium fulvum specifically induces a hypersensitive response in tomato genotypes carrying the complementary resistance gene Cf-9. The total chemical syntheses of this 28-residue AVR9 peptide containing three disulfide bonds, and of three mutant peptides [R8K]AVR9, [F10A]AVR9 and [F21A]AVR9, have been accomplished. The syntheses were carried out using a stepwise solid-phase approach based on tBoc chemistry. The disulfide bridges were formed by air oxidation. The correctness of the chemical structure of all folded synthetic peptides was confirmed by combined NMR and MS analyses. The biological activity and a number of physicochemical properties of folded synthetic AVR9 are identical to those of native fungal 28-residue AVR9. The overall conformations of the folded synthetic mutant peptides were comparable to that of synthetic wild-type AVR9 as demonstrated by NMR spectroscopy. Mutant [R8K]AVR9 showed a threefold higher, and mutant [F10A]AVR9 a threefold lower necrosis-inducing activity when compared to synthetic wild-type AVR9. However, mutant [F21A]AVR9 showed hardly any necrosis-inducing activity. Affinity for polyclonal antibodies raised against native fungal AVR9 is positively correlated with the necrosis-inducing activity of the synthetic AVR9 peptides ([R8K]AVR9 > wild-type AVR9 > [F10A]AVR9 > [F21A]AVR9).
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- 2009
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14. Vasoactive intestinal contractor (VIC) peptide structure in solution as determinated by proton NMR
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A Aumelas, E Mahé, B Perly, E Brun, Laurent Chiche, P Berthault, P Sizun, and D Le Nguyen
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chemistry.chemical_classification ,chemistry.chemical_compound ,Crystallography ,Nuclear magnetic resonance ,chemistry ,Hydrogen bond ,Amide ,Vasoactive intestinal contractor ,Proton NMR ,Peptide ,VIC peptide ,Acetonitrile ,Biochemistry - Abstract
The Vasoactive Intestinal Contractor peptide has been synthesized and studied by 1 H NMR in 50/50 acetonitrile/water mixture. All spin systems were identified and assigned with the aid of 2D experiments. Modeling was performed with constraints obtained by NOEs. Some distances used in modeling were calculated from build-up data. Kinetic exchange of the amide protons showed that the 9-15 helical segment is stabilized by at least three hydrogen bonds. The proposed structure is compared with those of Nle-7 endothelin and Sarafotoxin-S6b previously obtained in same conditions.
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- 1992
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15. Study of the conformation in solution of the trypsin binding loop of the synthetic bis-headed inhibitor TCPI. Combination of distance geometry, distance driven dynamics and restrained molecular dynamics
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André Padilla, Laurent Chiche, B. Castro, D. Le Nguyen, and Annie Heitz
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chemistry.chemical_classification ,biology ,Stereochemistry ,Chemistry ,Dynamics (mechanics) ,Peptide ,Trypsin ,Biochemistry ,Distance geometry ,Loop (topology) ,Crystallography ,Molecular dynamics ,Carboxypeptidase A ,biology.protein ,medicine ,Two-dimensional nuclear magnetic resonance spectroscopy ,medicine.drug - Abstract
The TCPI peptide which inhibits both trypsin and carboxypeptidase A has been chemically engineered by modification of the EETI-II inhibitor. The solution conformation of TCPI has been studied by 2D NMR and shown to be very close to those of other squash inhibitors. To evaluate the conformational mobility of the trypsin binding loop of TCPI in solution, distance driven dynamics and restrained molecular dynamics calculations were performed on distance geometry models. Only limited deviations of the binding loop from its location in the EETI-II/trypsin complex crystals were detected.
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- 1991
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16. Molecular recognition between serine proteases and new bioactive microproteins with a knotted structure
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A. Favel, Annie Heitz, M. A. Coletti-Previero, Bertrand Castro, R.-A. Boigegrain, Laurent Chiche, and D. Le Nguyen
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chemistry.chemical_classification ,Binding Sites ,Chymotrypsin ,biology ,Protein Conformation ,Chemistry ,Stereochemistry ,Molecular Sequence Data ,Peptide ,General Medicine ,Trypsin ,Biochemistry ,Carboxypeptidase ,Kinetics ,Protein structure ,biology.protein ,Carboxypeptidase A ,medicine ,Amino Acid Sequence ,Trypsin Inhibitors ,Peptide sequence ,Pancreatic elastase ,Plant Proteins ,medicine.drug - Abstract
Microproteins with proteinase inhibitory activity, 28 to 30 amino acids long, with 3 disulfide bridges have been isolated from Ecballium elaterium seeds. A peptide (EETI II) was isolated and behaved as a powerful trypsin inhibitor (Kd = 10(-11) to 10(-12) M). It was sequenced, chemically synthesized and the 3-D structure determined by 2-D 1H NMR. The information gained in the process enabled us to synthesize modified derivatives with inhibitory activity towards pancreatic elastase, chymotrypsin and human leucocyte elastase (Kd = 10(-7) to 10(-9) respectively). The most striking characteristic that appeared during the synthetic approach was the unfailing ability of the 28 amino acid peptides to refold and correctly close the 3 disulfide bridges, giving in each case an active compound. These disulfide bridges are assembled in a particular knotted structure, shared by few other bioactive peptides and called the 'knottin' structure. Molecular modeling of the peptide and a comparison with the other active molecules with similar topology allowed the synthesis of a chimaeric peptide, bearing 1 active site against a seryl-protease (trypsin), and 1 against a metallo-protease (carboxypeptidase A). The bis-headed peptide was able to inhibit both enzymes separately and concomitantly.
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- 1990
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17. PyBOP®: A new peptide coupling reagent devoid of toxic by-product
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Jacques Coste, Bertrand Castro, and D. Le-Nguyen
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chemistry.chemical_classification ,Bicyclic molecule ,Organic Chemistry ,Peptide ,Coupling reagent ,Biochemistry ,chemistry.chemical_compound ,PyBOP ,chemistry ,Hexafluorophosphate ,Drug Discovery ,By-product ,Organic chemistry ,Peptide bond ,Protecting group - Abstract
PyBOP® (benzotriazolyloxy-tris[pyrrolidino]-phosphonium hexafluorophosphate), an analog of BOP where dimethylamino groups are replaced with pyrrolidino, is the only analog exhibiting equivalent properties in peptide bond formation. It can be used instead of BOP for the sake of safety.
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- 1990
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18. Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9-39)
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R. Magous, J.‐p. Bali, C. Jarrousse, B. Millat, F. Borie, S. E. Ayachi, K. Sasaki, and D. Le Nguyen
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Adult ,Male ,endocrine system ,medicine.medical_specialty ,Contraction (grammar) ,Physiology ,medicine.drug_class ,Colon ,Molecular Sequence Data ,Glucagon-Like Peptides ,Motility ,Biology ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Protein Precursors ,Antrum ,Cells, Cultured ,Aged ,Aged, 80 and over ,Gastric emptying ,Dose-Response Relationship, Drug ,Sequence Homology, Amino Acid ,Endocrine and Autonomic Systems ,digestive, oral, and skin physiology ,Glicentin ,Gastroenterology ,Antagonist ,Biological activity ,Muscle, Smooth ,Middle Aged ,Receptor antagonist ,Glucagon ,Glucagon-like peptide-1 ,Peptide Fragments ,Endocrinology ,Female ,hormones, hormone substitutes, and hormone antagonists ,Muscle Contraction - Abstract
UNLABELLED Glicentin and glucagon-like peptide-1 (7-36) amide (GLP-1) are gut hormones released during digestion. Glicentin and GLP-1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP-1, and if their motility is dependent upon these digestive hormones. METHODS Twenty-two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed. RESULTS Glicentin caused a dose-related contraction of SMC, when GLP-1 determined a contraction of weak amplitude. Exendin-(9-39), described as a GLP-1 receptor antagonist, inhibited contraction due to glicentin or GLP-1. In contrast, on antral SMC from rabbit, GLP-1 exerts neither relaxation nor contraction; however, exendin-(9-39) dose dependently reduced the contractile activity of glicentin [glicentin EC(50) = 5 pM, exendin-(9-39) pA(2) = -9.36]. CONCLUSIONS The circular muscle from the human colon is a target tissue for glicentin and GLP-1. Whereas glicentin is a long-life digestive hormone which would contribute to segmental contraction, the biological activity of GLP-1 remains unknown on this tissue. On the digestive smooth muscle, exendin-(9-39) behaved as an antagonist for two members of the glucagon-receptor family, GLP-1 and glicentin.
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- 2005
19. Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine
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D. Le-Nguyen, Dominique Bataille, S. Pellissier, K. Sasaki, and C. Jarrousse
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Male ,medicine.medical_specialty ,Physiology ,GLIC ,Glucagon-Like Peptides ,Ileum ,Biology ,Jejunum ,chemistry.chemical_compound ,Eating ,Internal medicine ,Intestine, Small ,medicine ,Animals ,Protein Precursors ,Rats, Wistar ,Gastric emptying ,Endocrine and Autonomic Systems ,digestive, oral, and skin physiology ,Glicentin ,Gastroenterology ,Glucagon ,Small intestine ,Peptide Fragments ,Rats ,Oxyntomodulin ,Endocrinology ,medicine.anatomical_structure ,Postprandial ,chemistry ,Duodenum ,Gastrointestinal Motility - Abstract
Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33-69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three- to fourfold increase of the preprandial OXM–GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P
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- 2004
20. Solid-phase synthesis, conformational analysis, and biological activity of AVR9 elicitor peptides of the fungal tomato pathogen Cladosporium fulvum
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E, Mahé, P, Vossen, H W, Van den Hooven, D, Le-Nguyen, J, Vervoort, and P J, De Wit
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Peptide Biosynthesis ,Protein Folding ,Magnetic Resonance Spectroscopy ,Time Factors ,Blotting, Western ,Hydrogen-Ion Concentration ,Mass Spectrometry ,Fungal Proteins ,Necrosis ,Solanum lycopersicum ,Electrophoresis, Polyacrylamide Gel ,Cladosporium ,Chromatography, High Pressure Liquid ,Plant Proteins - Abstract
The race-specific peptide elicitor AVR9 of the fungal pathogen Cladosporium fulvum specifically induces a hypersensitive response in tomato genotypes carrying the complementary resistance gene Cf-9. The total chemical syntheses of this 28-residue AVR9 peptide containing three disulfide bonds, and of three mutant peptides [R8K]AVR9, [F10A]AVR9 and [F21A]AVR9, have been accomplished. The syntheses were carried out using a stepwise solid-phase approach based on tBoc chemistry. The disulfide bridges were formed by air oxidation. The correctness of the chemical structure of all folded synthetic peptides was confirmed by combined NMR and MS analyses. The biological activity and a number of physicochemical properties of folded synthetic AVR9 are identical to those of native fungal 28-residue AVR9. The overall conformations of the folded synthetic mutant peptides were comparable to that of synthetic wild-type AVR9 as demonstrated by NMR spectroscopy. Mutant [R8K]AVR9 showed a threefold higher, and mutant [F10A]AVR9 a threefold lower necrosis-inducing activity when compared to synthetic wild-type AVR9. However, mutant [F21A]AVR9 showed hardly any necrosis-inducing activity. Affinity for polyclonal antibodies raised against native fungal AVR9 is positively correlated with the necrosis-inducing activity of the synthetic AVR9 peptides ([R8K]AVR9wild-type AVR9[F10A]AVR9[F21A]AVR9).
- Published
- 1999
21. Glicentin and oxyntomodulin modulate both the phosphoinositide and cyclic adenosine monophosphate signaling pathways in gastric myocytes
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G, Rodier, R, Magous, T, Mochizuki, D, Le Nguyen, J, Martinez, J P, Bali, D, Bataille, C, Jarrousse, and R, Geneviève
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Colforsin ,Glicentin ,Glucagon-Like Peptides ,Muscle, Smooth ,Inositol 1,4,5-Trisphosphate ,In Vitro Techniques ,Glucagon ,Phosphatidylinositols ,Peptide Fragments ,Pertussis Toxin ,Oxyntomodulin ,Type C Phospholipases ,Cyclic AMP ,Pyloric Antrum ,Animals ,Calcium ,Carbachol ,Rabbits ,Virulence Factors, Bordetella ,Protein Precursors ,Muscle Contraction ,Signal Transduction - Abstract
We have investigated the transduction pathways mediating the contractile effect of two glucagon-containing peptides, glicentin (GLIC) and oxyntomodulin (OXM), on smooth muscle cells isolated from rabbit antrum. Low concentrations of GLIC induced a biphasic and rapid (first phase at 5-8 sec) Ins(1,4,5)P3 production. By comparison, higher concentrations of OXM or OXM(19-37) were required to obtain biphasic time-courses of Ins(1,4,5)P3 production. In a Ca2+ free medium, the first phase of Ins(1,4,5)P3 production induced by GLIC or OXM was maintained, while the second phase disappeared. In saponin-permeabilized cells, all three peptides induced cell contraction with similar efficacies and potencies. Exogenous Ins(1,4,5)P3 mimicked the contractile effect of the peptides and heparin, which inhibits the Ins(1,4,5)P3 binding to its receptor, prevented contraction stimulated by each effector. We conclude that a Ca2+ mobilization from the intracellular stores is essential in the contractile effects of GLIC and OXM. Using the fluo-3 probe, a [Ca2+]i increase was observed in the presence of GLIC, OXM, or OXM(19-37). The three peptides reduced by 30-40% the cAMP content of cells stimulated by forskolin. This effect was pertussis toxin sensitive as demonstrated with OXM(19-37). Our data constitute important clues for the existence in smooth muscle cells of receptor(s) specific for the GLIC/OXM hormones, coupled via G protein(s) to both Ca2+ and cAMP pathways.
- Published
- 1999
22. The disulfide folding pathway of Ecballium elaterium trypsin inhibitor II (EETI II)
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R. Dafniet, Bertrand Castro, Annie Heitz, D. Le Nguyen, L. Alfazema, M. El Hajji, and E. Mahé
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Folding (chemistry) ,biology ,Chemistry ,Stereochemistry ,Trypsin inhibitor ,Disulfide bond ,biology.organism_classification ,Ecballium elaterium - Published
- 1995
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23. 5-Hydroxytryptamine1A receptor synthetic peptides. Mechanisms of adenylyl cyclase inhibition
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A, Varrault, D, Le Nguyen, S, McClue, B, Harris, P, Jouin, and J, Bockaert
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Male ,Molecular Sequence Data ,Moths ,Hippocampus ,Protein Structure, Secondary ,Cell Line ,Mice ,GTP-Binding Proteins ,Animals ,Humans ,Amino Acid Sequence ,Virulence Factors, Bordetella ,Rats, Wistar ,8-Hydroxy-2-(di-n-propylamino)tetralin ,Cell Membrane ,Colforsin ,3T3 Cells ,Peptide Fragments ,Clone Cells ,Rats ,Kinetics ,Pertussis Toxin ,Guanosine 5'-O-(3-Thiotriphosphate) ,Receptors, Serotonin ,Adenylyl Cyclase Inhibitors ,Adenylate Cyclase Toxin ,Guanosine Triphosphate - Abstract
The 5-hydroxytryptamine1A receptor (5-HT1AR) is a G-protein-coupled receptor negatively coupled to adenylyl cyclase (AC). We have studied the functional domains of 5-HT1AR using synthetic peptides to block or mimic receptor function. The entire second intracellular loop (5-HT1AR-i2) and the carboxyl end of the third intracellular loop (5-HT1AR-i3-C) strongly inhibited forskolin-stimulated AC activity. These effects were not additive with those of 5-HT. Like 5-HT, the peptides 5-HT1AR-i3-C and -i2 weakly inhibited AIF4- and Mn2+ stimulated AC activity. 5-HT1AR binding assays indicated that peptides could interact with the same G-protein pool as the 5-HT1AR. 5-HT1AR-i3-C- and -i2-stimulated [35S]guanosine 5'-O-(thiotriphosphate) binding on Go/Gi proteins. Only 5-HT1AR-i3-C partially adopted an alpha-helical conformation in solution. These data show that different domains in the 5-HT1AR second and third intracellular loops can couple to and activate Gi proteins in order to mediate AC inhibition. Peptide-induced AC inhibition was not sensitive to pertussis toxin as opposed to the 5-HT1AR-mediated effect. Our data show that the 5-HT1AR and the 5-HT1AR peptides activate Gi proteins in a slightly different manner.
- Published
- 1994
24. TPyClU: A new peptide coupling reagent
- Author
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F. Roux, D. Le-Nguyen, A. Loffet, Eric Frérot, J. Coste, and P. Jouin
- Subjects
chemistry.chemical_classification ,Chemistry ,Peptide ,Coupling reagent ,Combinatorial chemistry - Published
- 1992
- Full Text
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25. Effects of early embryonic bursectomy and opotherapic substitution on the functional development of the adrenocorticotropic axis
- Author
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M, Guellati, F, Ramade, D, Le Nguyen, F, Ibos, and J D, Bayle
- Subjects
Bursa of Fabricius ,Adrenocorticotropic Hormone ,Stress, Physiological ,Molecular Sequence Data ,Adrenal Cortex ,Animals ,Amino Acid Sequence ,Chick Embryo ,Corticosterone ,Chickens ,Oligopeptides - Abstract
Functional development of the adrenocorticotropic axis was inferred from plasma ACTH and corticosterone levels in intact and embryonically bursectomized (BFX) embryos and chicks from 8 days before to 56 days after hatch. Bursectomy was surgically made at 80 h of incubation and resulted in various alterations in developing adrenocorticotropic axis: ether stress-induced hormonal stimulation could be detected more precociously in BFX (day-6) than in intact embryos; the non stress-responsive period of newly hatched controls did not appear in BFX chicks; BFX young adult chicken exhibited quite smaller responses to stress than controls. In ovo injection of bursin (Lys-His-Gly-NH2) to 6- and 9-days old BFX embryos could restore normal adrenocorticotropic development provided convenient doses of tripeptide were used: administration of 100 fg or 100 pg of bursin was effective to restore normal hormonal levels at all stages studied whereas 100 micrograms was effective at embryonic stages only. The tripeptide Lys-His-Gly-NH2 is suggested as a possible signal from the immune B system directed at the hypothalamo-hypophysial-adrenocortical axis.
- Published
- 1991
26. Are several G proteins involved in the different effects of endothelin-1 in mouse striatal astrocytes?
- Author
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Joël Prémont, D. Le Nguyen, Odile Durieu-Trautmann, Philippe Marin, J. C. Delumeau, Arthur Donny Strosberg, and Pierre Olivier Couraud
- Subjects
G protein ,Inositol Phosphates ,Stimulation ,Mice, Inbred Strains ,Biology ,Biochemistry ,Cellular and Molecular Neuroscience ,Mice ,Cytosol ,GTP-Binding Proteins ,medicine ,Cyclic AMP ,Animals ,Inositol phosphate ,chemistry.chemical_classification ,Endothelins ,Osmolar Concentration ,Embryo, Mammalian ,Endothelin 1 ,Corpus Striatum ,Cell biology ,medicine.anatomical_structure ,chemistry ,Astrocytes ,Second messenger system ,Neuroglia ,Calcium ,Signal transduction ,Endothelin receptor - Abstract
High-affinity specific receptors of endothelin (ET-1) were identified on primary cultures of mouse embryo striatal astrocytes by binding experiments performed with 125I-ET-1. Stimulation of production of inositol phosphates, a biphasic increase of the intracellular calcium concentration, and inhibition of cyclic AMP accumulation were observed in the same cells under ET-1 stimulation. Pretreatment of these cells with Bordetella pertussis toxin affected these effects to different extends, an observation suggesting that they are mediated by multiple transduction pathways, possibly involving several guanine nucleotide-binding proteins.
- Published
- 1991
27. ChemInform Abstract: PyBOP(R) (I): A New Peptide Coupling Reagent Devoid of Toxic By-Product
- Author
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Jacques Coste, D. Le-Nguyen, and Bertrand Castro
- Subjects
chemistry.chemical_classification ,PyBOP ,chemistry.chemical_compound ,chemistry ,By-product ,Peptide ,General Medicine ,Coupling reagent ,Combinatorial chemistry - Published
- 1990
- Full Text
- View/download PDF
28. EETI II (Ecballium elaterium Trypsin Inhibitor II) as a Vehicle for New Functions
- Author
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D. Le-Nguyen, B. Castro, A. Favel, H. Mattras, and M.A. Coletti-Previero
- Subjects
biology ,Chemistry ,Trypsin inhibitor ,Pharmacology ,biology.organism_classification ,Ecballium elaterium - Published
- 1990
- Full Text
- View/download PDF
29. Fragments coupling in peptide synthesis I. The basis of quantitative relationships between structure and epimerization
- Author
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D. Le Nguyen, Bertrand Castro, and Jean-Robert Dormoy
- Subjects
Coupling (electronics) ,chemistry.chemical_compound ,Chromatography ,Basis (linear algebra) ,Chemistry ,Computational chemistry ,Organic Chemistry ,Drug Discovery ,Peptide synthesis ,Epimer ,Biochemistry - Published
- 1978
- Full Text
- View/download PDF
30. Purification from human plasma of a tetrapeptide that potentiates insulin-like growth factor-I activity in chick embryo cartilage
- Author
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M. Becchi, F. Maachi, P. Nabet, M.H. Heulin, J. Straczek, F. Belleville, D. Le Nguyen, and Deleage, Gilbert
- Subjects
animal structures ,medicine.medical_treatment ,Molecular Sequence Data ,Biophysics ,Peptide ,Chick Embryo ,Peptide purification ,Biochemistry ,Mass Spectrometry ,Glycosaminoglycan synthesis ,Insulin-like growth factor ,chemistry.chemical_compound ,Biosynthesis ,Structural Biology ,Genetics ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Chromatography, High Pressure Liquid ,Glycosaminoglycans ,chemistry.chemical_classification ,Tetrapeptide ,Edman degradation ,integumentary system ,Cartilage ,Protein primary structure ,Electrophoresis, Capillary ,Embryo ,Insulin-like growth factor I ,Cell Biology ,Chick embryo chondrocyte ,Recombinant Proteins ,Extracellular Matrix ,medicine.anatomical_structure ,chemistry ,embryonic structures ,Human plasma ,Oligopeptides ,Wound repair - Abstract
Human plasma has been shown to contain a low molecular weight factor that potentiates human IGF-I stimulation of glycosaminoglycan synthesis in chick embryo cartilage. The peptide was purified and characterized by Edman degradation and electrospray mass spectrometry. The primary structure determined was: Trp-Gly-His-Glu. A homologous synthetic peptide similarly promoted matrix biosynthesis in cartilage exposed to IGF-I.Human plasma has been shown to contain a low molecular weight factor that potentiates human IGF-I stimulation of glycosaminoglycan synthesis in chick embryo cartilage. The peptide was purified and characterized by Edman degradation and electrospray mass spectrometry. The primary structure determined was: Trp-Gly-His-Glu. A homologous synthetic peptide similarly promoted matrix biosynthesis in cartilage exposed to IGF-I.
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- View/download PDF
31. 1H 2D NMR and distance geometry study of the folding of Ecballium elaterium trypsin inhibitor, a member of the squash inhibitors family
- Author
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A, Heitz, L, Chiche, D, Le-Nguyen, and B, Castro
- Subjects
Models, Molecular ,Magnetic Resonance Spectroscopy ,Protein Conformation ,Molecular Sequence Data ,Amino Acid Sequence ,Plants ,Trypsin Inhibitors ,Hydrogen ,Plant Proteins - Abstract
The solution conformation of synthetic Ecballium elaterium trypsin inhibitor II, a 28-residue peptide with 3 disulfide bridges, has been studied by 1H 2D NMR measurements. Secondary structure elements were determined: a miniantiparallel beta-sheet Met 7-Cys 9 and Gly 25-Cys 27, a beta-hairpin 20-28 with beta-turn 22-25, and two tight turns Asp 12-Cys 15 and Leu 16-Cys 19. A set of interproton distance restraints deduced from two-dimensional nuclear Overhauser enhancement spectra and 13 phi backbone torsion angles restraints were used as the basis of three-dimensional structure computations including disulfide bridges arrangement by using distance geometry calculations. Computations for the 15 possible S-S linkage combinations lead to the proposal of the array 2-19, 9-21, 15-27 as the most probable structure for EETI II.
- Published
- 1989
32. [Glucagon is processed to the (19-29) fragment at the level of the hepatocyte membrane]
- Author
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P, Blache, A, Kervran, M, Dufour, J, Martinez, D, Le-Nguyen, S, Lotersztajn, C, Pavoine, F, Pecker, and D, Bataille
- Subjects
Liver ,Cell Membrane ,Radioimmunoassay ,Animals ,Peptide Chain Termination, Translational ,Glucagon ,Chromatography, High Pressure Liquid ,Peptide Fragments ,Rats - Abstract
Upon incubation with hepatic plasma membranes, glucagon is processed into its (19-29) C-terminal fragment. This suggests that, in physiological conditions, glucagon is processed in a target tissue at the level of its Arg17-Arg18 basic doublet, leading to the production of a fragment which is known to display an original biological specificity, namely the modulation of the calcium pump present in hepatocyte plasma membrane.
- Published
- 1989
33. ChemInform Abstract: Use of Carboethoxysulfenyl Chloride for Disulfide Bond Formation
- Author
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D. LE-NGUYEN and J. RIVIER
- Subjects
General Medicine - Published
- 1986
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- View/download PDF
34. Crystallization and preliminary X-ray study of porcine trypsin, free and complexed with Ecballium elaterium trypsin inhibitor, a member of the squash inhibitors family
- Author
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B. Bachet, B. Castro, D. Le-Nguyen, Jean-Paul Mornon, Christine Gaboriaud, and Marie-Christine Vaney
- Subjects
Stereochemistry ,Protein Conformation ,Swine ,Trypsin inhibitor ,Peptide ,law.invention ,X-Ray Diffraction ,Structural Biology ,law ,medicine ,Animals ,Trypsin ,Crystallization ,Molecular Biology ,Plant Proteins ,chemistry.chemical_classification ,Crystallography ,biology ,Elaterium ,X-ray ,biology.organism_classification ,Ecballium elaterium ,chemistry ,Orthorhombic crystal system ,Trypsin Inhibitors ,medicine.drug - Abstract
Porcine trypsin has been crystallized either free or complexed with synthetic Ecballium elaterium trypsin inhibitor II, a 28-residue peptide with three disulfide bridges. The crystals diffract beyond 2.0 A. Crystals are orthorhombic, space group P2(1)2(1)2(1), with cell dimensions a = 77.32 A, b = 53.81 A, c = 46.91 A, for the free trypsin, and a = 62.25 A, b = 62.27 A, c = 84.66 A for the complex with E. elaterium trypsin inhibitor II.
- Published
- 1989
35. ChemInform Abstract: Renin Substrates. Part 1. Liquid-Phase Synthesis of the Equine Sequence with Benzotriazolyloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)
- Author
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D. LE NGUYEN, R. SEYER, A. HEITZ, and B. CASTRO
- Subjects
General Medicine - Published
- 1985
- Full Text
- View/download PDF
36. Renin substrates. Part 1. Liquid-phase synthesis of the equine sequence with benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP)
- Author
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Bertrand Castro, Annie Heitz, D. Le Nguyen, and René Seyer
- Subjects
chemistry.chemical_compound ,chemistry ,Stereochemistry ,Hexafluorophosphate ,Yield (chemistry) ,Liquid phase ,Sequence (biology) ,Nuclear magnetic resonance spectroscopy ,Phosphonium ,BOP reagent ,Medicinal chemistry ,Histidine - Abstract
The tetradecapeptide Ac-Asp1-Arg2-Val3-Tyr4-lle5-His6-Pro7-Phe8-His9-Leu10-Leu11-Val12-Tyr13-Ser14-OH has been synthesized by a three-segment coupling strategy. All the coupling steps were carried out with benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent). Histidine was incorporated in good yield by using Boc(Nim-Boc)histidine (DCHA).
- Published
- 1985
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- View/download PDF
37. The Safety and Feasibility of Ambulatory Minimally Invasive Partial Nephrectomy: A Systematic Review and Meta-Analysis.
- Author
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Paynter A, Uy M, Millan B, Le Nguyen D, Bansal R, and Shayegan B
- Subjects
- Humans, Postoperative Complications etiology, Patient Satisfaction, Patient Readmission statistics & numerical data, Length of Stay, Nephrectomy methods, Nephrectomy adverse effects, Ambulatory Surgical Procedures adverse effects, Ambulatory Surgical Procedures methods, Minimally Invasive Surgical Procedures methods, Minimally Invasive Surgical Procedures adverse effects, Feasibility Studies
- Abstract
Purpose: Emerging evidence supports the use of minimally invasive partial nephrectomy (MIPN) in ambulatory settings. We conducted a systematic review and meta-analysis to evaluate differences in perioperative characteristics, complication/readmission rates and satisfaction/cost data between ambulatory and standard-length discharge (SLD) MIPN. Methods: This study was prospectively registered in PROSPERO (CRD42023429854). A systematic literature search of PubMed, Embase, and Web of Science databases was conducted, including studies comparing ambulatory MIPN vs SLD MIPN for patients with renal masses. Studies were assessed for quality using the Methodological Index for Non-Randomized Studies score. Meta-analysis was performed for comparative studies, and non-comparative studies were included narratively. Results: Eleven studies were included with a pooled population of 20,548 patients, of which 1,419 (7%) had a length of stay less than 1 day and were considered the ambulatory group. There were no significant differences in the total complication rates (RR: 0.50, 95% CI: 0.24, 1.04; p = 0.06) or 30-day readmission rates (RR: 0.87, 95% CI: 0.56, 1.35; p = 0.53) between the ambulatory and SLD groups. There were fewer >3 Clavien-Dindo complications in the ambulatory group (RR: 0.34, 95% CI: 0.19, 0.59; p = 0.0002). Few studies reported average health care cost and patient satisfaction. Conclusions: In appropriately selected patients, ambulatory MIPN is safe and feasible. Future studies are needed to quantify cost and patient satisfaction differences and further identify appropriate patient selection criteria for ambulatory MIPN.
- Published
- 2024
- Full Text
- View/download PDF
38. Computational design of protein-based inhibitors of Plasmodium vivax subtilisin-like 1 protease.
- Author
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Bastianelli G, Bouillon A, Nguyen C, Le-Nguyen D, Nilges M, and Barale JC
- Subjects
- Catalysis, Crystallography, X-Ray, Humans, Malaria, Vivax pathology, Plasmodium vivax metabolism, Protein Binding, Protein Conformation, Protozoan Proteins genetics, Sequence Homology, Amino Acid, Subtilisins genetics, Malaria, Vivax metabolism, Molecular Docking Simulation, Plasmodium vivax chemistry, Protozoan Proteins chemistry, Subtilisins chemistry
- Abstract
Background: Malaria remains a major global health concern. The development of novel therapeutic strategies is critical to overcome the selection of multiresistant parasites. The subtilisin-like protease (SUB1) involved in the egress of daughter Plasmodium parasites from infected erythrocytes and in their subsequent invasion into fresh erythrocytes has emerged as an interesting new drug target., Findings: Using a computational approach based on homology modeling, protein-protein docking and mutation scoring, we designed protein-based inhibitors of Plasmodium vivax SUB1 (PvSUB1) and experimentally evaluated their inhibitory activity. The small peptidic trypsin inhibitor EETI-II was used as scaffold. We mutated residues at specific positions (P4 and P1) and calculated the change in free-energy of binding with PvSUB1. In agreement with our predictions, we identified a mutant of EETI-II (EETI-II-P4LP1W) with a Ki in the medium micromolar range., Conclusions: Despite the challenges related to the lack of an experimental structure of PvSUB1, the computational protocol we developed in this study led to the design of protein-based inhibitors of PvSUB1. The approach we describe in this paper, together with other examples, demonstrates the capabilities of computational procedures to accelerate and guide the design of novel proteins with interesting therapeutic applications.
- Published
- 2014
- Full Text
- View/download PDF
39. N-truncated Aβ peptides in complex fluids unraveled by new specific immunoassays.
- Author
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Ranaldi S, Caillava C, Promé S, Rubrecht L, Cobo S, Salvetat N, du Paty E, Galea P, Aldrian G, Le Nguyen D, Krolak-Salmon P, Molina F, Laune D, Checler F, Fareh J, and Abraham JD
- Subjects
- Aged, Amyloid beta-Peptides cerebrospinal fluid, Humans, Immunoassay, Middle Aged, Peptide Fragments cerebrospinal fluid, Phosphorylation, Pilot Projects, tau Proteins cerebrospinal fluid, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Peptides metabolism, Dementia metabolism, Peptide Fragments metabolism
- Abstract
Previous studies have highlighted the potential physiopathological and diagnostic role of N- and C-terminally truncated amyloid-β (Aβ) peptides in Alzheimer's disease. However, our knowledge about their production remains incomplete, in part due to the lack of very specific and sensitive tools for their detection. We thus developed specific monoclonal antibodies that target either Aβ11-x or Aβ17-x species, which result from the combined cleavages by β/γ- or α/γ-secretases, respectively. The presence of Aβ peptides truncated at residue 11 and 17 peptides was qualitatively and quantitatively assessed, using surface enhanced laser desorption ionization-time of flight mass spectrometry and xMAP (Multi-Analyte Profiling) immunoassays, in the supernatant of HEK293 cells that overexpress wild type or mutant Aβ protein precursor or in which α- and β-secretase activities had been modulated. Our results show a differential secretion of Aβ11-40 and Aβ17-40 species by these HEK293 cell lines. Finally, Aβ11-40 concentration in human cerebrospinal fluid (measured with the new xMAP immunoassays) from a first pilot study was higher in cerebrospinal fluid samples from patients with Alzheimer's disease than in samples from patients with other types of dementia., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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40. Computational reverse-engineering of a spider-venom derived peptide active against Plasmodium falciparum SUB1.
- Author
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Bastianelli G, Bouillon A, Nguyen C, Crublet E, Pêtres S, Gorgette O, Le-Nguyen D, Barale JC, and Nilges M
- Subjects
- Amino Acid Sequence, Biocatalysis drug effects, Merozoites cytology, Merozoites drug effects, Molecular Dynamics Simulation, Molecular Sequence Data, Peptides chemistry, Plasmodium falciparum drug effects, Protein Binding drug effects, Protozoan Proteins chemistry, Protozoan Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Solvents, Spider Venoms chemistry, Subtilisin metabolism, Peptides pharmacology, Plasmodium falciparum metabolism, Protein Engineering methods, Protozoan Proteins antagonists & inhibitors, Reverse Genetics methods, Spider Venoms pharmacology
- Abstract
Background: Psalmopeotoxin I (PcFK1), a protein of 33 aminoacids derived from the venom of the spider Psalmopoeus Cambridgei, is able to inhibit the growth of Plasmodium falciparum malaria parasites with an IC50 in the low micromolar range. PcFK1 was proposed to act as an ion channel inhibitor, although experimental validation of this mechanism is lacking. The surface loops of PcFK1 have some sequence similarity with the parasite protein sequences cleaved by PfSUB1, a subtilisin-like protease essential for egress of Plasmodium falciparum merozoites and invasion into erythrocytes. As PfSUB1 has emerged as an interesting drug target, we explored the hypothesis that PcFK1 targeted PfSUB1 enzymatic activity., Findings: Molecular modeling and docking calculations showed that one loop could interact with the binding site of PfSUB1. The calculated free energy of binding averaged -5.01 kcal/mol, corresponding to a predicted low-medium micromolar constant of inhibition. PcFK1 inhibited the enzymatic activity of the recombinant PfSUB1 enzyme and the in vitro P. falciparum culture in a range compatible with our bioinformatics analysis. Using contact analysis and free energy decomposition we propose that residues A14 and Q15 are important in the interaction with PfSUB1., Conclusions: Our computational reverse engineering supported the hypothesis that PcFK1 targeted PfSUB1, and this was confirmed by experimental evidence showing that PcFK1 inhibits PfSUB1 enzymatic activity. This outlines the usefulness of advanced bioinformatics tools to predict the function of a protein structure. The structural features of PcFK1 represent an interesting protein scaffold for future protein engineering.
- Published
- 2011
- Full Text
- View/download PDF
41. Cell-permeable peptide-based disruption of endogenous PKA-AKAP complexes: a tool for studying the molecular roles of AKAP-mediated PKA subcellular anchoring.
- Author
-
Faruque OM, Le-Nguyen D, Lajoix AD, Vives E, Petit P, Bataille D, and Hani EH
- Subjects
- Animals, Cell Line, Cyclic AMP metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Fluorescent Antibody Technique, Glucagon metabolism, Glucose metabolism, Immunoprecipitation, Insulin metabolism, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Phosphorylation, Protein Binding, Protein Transport, Rats, Time Factors, tat Gene Products, Human Immunodeficiency Virus metabolism, A Kinase Anchor Proteins metabolism, Cell Membrane Permeability, Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit metabolism, Insulin-Secreting Cells enzymology, Nuclear Proteins metabolism, Peptide Fragments metabolism, Signal Transduction
- Abstract
Stimulation of numerous G protein-coupled receptors leads to the elevation of intracellular concentrations of cAMP, which subsequently activates the PKA pathway. Specificity of the PKA signaling module is determined by a sophisticated subcellular targeting network that directs the spatiotemporal activation of the kinase. This specific compartmentalization mechanism occurs through high-affinity interactions of PKA with A-kinase anchoring proteins (AKAPs), the role of which is to target the kinase to discrete subcellular microdomains. Recently, a peptide designated "AKAPis" has been proposed to competitively inhibit PKA-AKAP interactions in vitro. We therefore sought to characterize a cell-permeable construct of the AKAPis inhibitor and use it as a tool to characterize the impact of PKA compartmentalization by AKAPs. Using insulin-secreting pancreatic beta-cells (INS-1 cells), we showed that TAT-AKAPis (at a micromolar range) dose dependently disrupted a significant fraction of endogenous PKA-AKAP interactions. Immunoflurescent analysis also indicated that TAT-AKAPis significantly affected PKA subcellular localization. Furthermore, TAT-AKAPis markedly attenuated glucagon-induced phosphorylations of p44/p42 MAPKs and cAMP response element binding protein, which are downstream effectors of PKA. In parallel, TAT-AKAPis dose dependently inhibited the glucagon-induced potentiation of insulin release. Therefore, AKAP-mediated subcellular compartmentalization of PKA represents a key mechanism for PKA-dependent phosphorylation events and potentiation of insulin secretion in intact pancreatic beta-cells. More interestingly, our data highlight the effectiveness of the cell-permeable peptide-mediated approach to monitoring in cellulo PKA-AKAP interactions and delineating PKA-dependent phosphorylation events underlying specific cellular responses.
- Published
- 2009
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- View/download PDF
42. Knottin cyclization: impact on structure and dynamics.
- Author
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Heitz A, Avrutina O, Le-Nguyen D, Diederichsen U, Hernandez JF, Gracy J, Kolmar H, and Chiche L
- Subjects
- Computer Simulation, Cyclization, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Cyclotides chemistry, Cystine Knot Motifs genetics, Drug Design, Macrocyclic Compounds chemistry, Models, Molecular
- Abstract
Background: Present in various species, the knottins (also referred to as inhibitor cystine knots) constitute a group of extremely stable miniproteins with a plethora of biological activities. Owing to their small size and their high stability, knottins are considered as excellent leads or scaffolds in drug design. Two knottin families contain macrocyclic compounds, namely the cyclotides and the squash inhibitors. The cyclotide family nearly exclusively contains head-to-tail cyclized members. On the other hand, the squash family predominantly contains linear members. Head-to-tail cyclization is intuitively expected to improve bioactivities by increasing stability and lowering flexibility as well as sensitivity to proteolytic attack., Results: In this paper, we report data on solution structure, thermal stability, and flexibility as inferred from NMR experiments and molecular dynamics simulations of a linear squash inhibitor EETI-II, a circular squash inhibitor MCoTI-II, and a linear analog lin-MCoTI. Strikingly, the head-to-tail linker in cyclic MCoTI-II is by far the most flexible region of all three compounds. Moreover, we show that cyclic and linear squash inhibitors do not display large differences in structure or flexibility in standard conditions, raising the question as to why few squash inhibitors have evolved into cyclic compounds. The simulations revealed however that the cyclization increases resistance to high temperatures by limiting structure unfolding., Conclusion: In this work, we show that, in contrast to what could have been intuitively expected, cyclization of squash inhibitors does not provide clear stability or flexibility modification. Overall, our results suggest that, for squash inhibitors in standard conditions, the circularization impact might come from incorporation of an additional loop sequence, that can contribute to the miniprotein specificity and affinity, rather than from an increase in conformational rigidity or protein stability. Unfolding simulations showed however that cyclization is a stabilizing factor in strongly denaturing conditions. This information should be useful if one wants to use the squash inhibitor scaffold in drug design.
- Published
- 2008
- Full Text
- View/download PDF
43. KNOTTIN: the knottin or inhibitor cystine knot scaffold in 2007.
- Author
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Gracy J, Le-Nguyen D, Gelly JC, Kaas Q, Heitz A, and Chiche L
- Subjects
- Cysteine chemistry, Internet, Proteins chemistry, Sequence Alignment standards, Sequence Analysis, Protein standards, Software, Cystine Knot Motifs, Databases, Protein
- Abstract
The KNOTTIN database provides standardized information on the small disulfide-rich proteins with a knotted topology called knottins or inhibitor cystine knots. Static pages present the essential historical or recent results about knottin discoveries, sequences, structures, syntheses, folding, functions, applications and bibliography. New tools, KNOTER3D and KNOTER1D, are provided to determine or predict if a user query (3D structure or sequence) is a knottin. These tools are now used to automate the database update. All knottin structures and sequences in the database are now standardized according to the knottin nomenclature based on loop lengths between knotted cysteines, and to the knottin numbering scheme. Therefore, the whole KNOTTIN database (sequences and structures) can now be searched using loop lengths, in addition to keyword and sequence (BLAST, HMMER) searches. Renumbered and structurally fitted knottin PDB files are available for download as well as renumbered sequences, sequence alignments and logos. The knottin numbering scheme is used for automatic drawing of standardized two-dimensional Colliers de Perles of any knottin structure or sequence in the database or provided by the user. The KNOTTIN database is available at http://knottin.cbs.cnrs.fr.
- Published
- 2008
- Full Text
- View/download PDF
44. Role of Asn(2) and Glu(7) residues in the oxidative folding and on the conformation of the N-terminal loop of apamin.
- Author
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Le-Nguyen D, Chiche L, Hoh F, Martin-Eauclaire MF, Dumas C, Nishi Y, Kobayashi Y, and Aumelas A
- Subjects
- Amino Acid Sequence, Animals, Apamin analogs & derivatives, Asparagine chemistry, Crystallography, X-Ray, Dimerization, Glutamic Acid chemistry, Hydrogen-Ion Concentration, In Vitro Techniques, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Proline chemistry, Protein Conformation, Protein Folding, Protein Structure, Quaternary, Solutions, Thermodynamics, Apamin chemistry
- Abstract
The X-ray structure of [N-acetyl]-apamin has been solved at 0.95 A resolution. It consists of an 1-7 N-terminal loop stabilized by an Asn-beta-turn motif (2-5 residues) and a helical structure spanning the 9-18 residues tightly linked together by two disulfide bonds. However, neither this accurate X-ray nor the available solution structures allowed us to rationally explain the unusual downfield shifts observed for the Asn(2) and Glu(7) amide signals upon Glu(7) carboxylic group ionization. Thus, apamin and its [N-acetyl], [Glu(7)Gln], [Glu(7)Asp], and [Asn(2)Abu] analogues and submitted to NMR structural studies as a function of pH. We first demonstrated that the Glu(7) carboxylate group is responsible for the large downfield shifts of the Asn(2) and Glu(7) amide signals. Then, molecular dynamics (MD) simulations suggested unexpected interactions between the carboxylate group and the Asn(2) and Glu(7) amide protons as well as the N-terminal alpha-amino group, through subtle conformational changes that do not alter the global fold of apamin. In addition, a structural study of the [Asn(2)Abu] analogue, revealed an essential role of Asn(2) in the beta-turn stability and the cis/trans isomerization of the Ala(5)-Pro(6) amide bond. Interestingly, this proline isomerization was shown to also depend on the ionization state of the Glu(7) carboxyl group. However, neither destabilization of the beta-turn nor proline isomerization drastically altered the helical structure that contains the residues essential for binding. Altogether, the Asn(2) and Glu(7) residues appeared essential for the N-terminal loop conformation and thus for the selective formation of the native disulfide bonds but not for the activity.
- Published
- 2007
- Full Text
- View/download PDF
45. Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II.
- Author
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Avrutina O, Schmoldt HU, Gabrijelcic-Geiger D, Le Nguyen D, Sommerhoff CP, Diederichsen U, and Kolmar H
- Subjects
- Alanine chemistry, Amino Acid Sequence, Arginine chemistry, Chromogranins chemistry, Cyclization, Cyclotides pharmacology, Lysine chemistry, Molecular Mimicry, Molecular Sequence Data, Protein Conformation, Cucurbitaceae enzymology, Cyclotides chemical synthesis, Trypsin metabolism
- Abstract
MCoTI-I and MCoTI-II from the seeds of Momordica cochinchinensis are inhibitors of trypsin-like proteases and the only known members of the large family of squash inhibitors that are cyclic and contain an additional loop connecting the amino- and the carboxy-terminus. To investigate the contribution of macrocycle formation to biological activity, we synthesized a set of open-chain variants of MCoTI-II that lack the cyclization loop and contain various natural and non-natural amino acid substitutions in the reactive-site loop. Upon replacement of P1 lysine residue #10 within the open-chain variant of MCoTI-II by the non-natural isosteric nucleo amino acid AlaG [beta-(guanin-9-yl)-L-alanine], a conformationally restricted arginine mimetic, residual inhibitory activity was detected, albeit reduced by four orders of magnitude. While the cyclic inhibitors MCoTI-I and MCoTI-II were found to be very potent trypsin inhibitors, with picomolar inhibition constants, the open-chain variants displayed an approximately 10-fold lower affinity. These data suggest that the formation of a circular backbone in the MCoTI squash inhibitors results in enhanced affinity and therefore is a determinant of biological activity.
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- 2005
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46. Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9-39).
- Author
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Ayachi SE, Borie F, Magous R, Sasaki K, le Nguyen D, Bali JP, Millat B, and Jarrousse C
- Subjects
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Cells, Cultured, Colon physiology, Dose-Response Relationship, Drug, Female, Glicentin, Glucagon genetics, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Humans, Male, Middle Aged, Molecular Sequence Data, Muscle Contraction physiology, Muscle, Smooth physiology, Peptide Fragments genetics, Protein Precursors genetics, Sequence Homology, Amino Acid, Colon drug effects, Glucagon pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Peptide Fragments pharmacology, Protein Precursors pharmacology
- Abstract
Unlabelled: Glicentin and glucagon-like peptide-1 (7-36) amide (GLP-1) are gut hormones released during digestion. Glicentin and GLP-1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP-1, and if their motility is dependent upon these digestive hormones., Methods: Twenty-two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed., Results: Glicentin caused a dose-related contraction of SMC, when GLP-1 determined a contraction of weak amplitude. Exendin-(9-39), described as a GLP-1 receptor antagonist, inhibited contraction due to glicentin or GLP-1. In contrast, on antral SMC from rabbit, GLP-1 exerts neither relaxation nor contraction; however, exendin-(9-39) dose dependently reduced the contractile activity of glicentin [glicentin EC(50) = 5 pM, exendin-(9-39) pA(2) = -9.36]., Conclusions: The circular muscle from the human colon is a target tissue for glicentin and GLP-1. Whereas glicentin is a long-life digestive hormone which would contribute to segmental contraction, the biological activity of GLP-1 remains unknown on this tissue. On the digestive smooth muscle, exendin-(9-39) behaved as an antagonist for two members of the glucagon-receptor family, GLP-1 and glicentin.
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- 2005
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47. Miniglucagon (MG)-generating endopeptidase, which processes glucagon into MG, is composed of N-arginine dibasic convertase and aminopeptidase B.
- Author
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Fontés G, Lajoix AD, Bergeron F, Cadel S, Prat A, Foulon T, Gross R, Dalle S, Le-Nguyen D, Tribillac F, and Bataille D
- Subjects
- Aminopeptidases antagonists & inhibitors, Aminopeptidases genetics, Animals, Calcium pharmacology, Cells, Cultured, Cobalt pharmacology, Endopeptidases genetics, Endopeptidases metabolism, Hypoglycemia metabolism, Metalloendopeptidases genetics, Mice, Phenanthrolines pharmacology, Protease Inhibitors pharmacology, Recombinant Proteins genetics, Recombinant Proteins metabolism, Substrate Specificity, Zinc pharmacology, Aminopeptidases metabolism, Glucagon biosynthesis, Glucagon metabolism, Islets of Langerhans enzymology, Metalloendopeptidases metabolism, Peptide Fragments biosynthesis
- Abstract
Miniglucagon (MG), the C-terminal glucagon fragment, processed from glucagon by the MG-generating endopeptidase (MGE) at the Arg17-Arg18 dibasic site, displays biological effects opposite to that of the mother-hormone. This secondary processing occurs in the glucagon- and MG-producing alpha-cells of the islets of Langerhans and from circulating glucagon. We first characterized the enzymatic activities of MGE in culture media from glucagon and MG-secreting alphaTC1.6 cells as made of a metalloendoprotease and an aminopeptidase. We observed that glucagon is a substrate for N-arginine dibasic convertase (NRDc), a metalloendoprotease, and that aminopeptidase B cleaves in vitro the intermediate cleavage products sequentially, releasing mature MG. Furthermore, immunodepletion of either enzyme resulted in the disappearance of the majority of MGE activity from the culture medium. We found RNAs and proteins corresponding to both enzymes in different cell lines containing a MGE activity (mouse alphaTC1.6 cells, rat hepatic FaO, and rat pituitary GH4C1). Using confocal microscopy, we observed a granular immunostaining of both enzymes in the alphaTC1.6 and native rat alpha-cells from islets of Langerhans. By immunogold electron microscopy, both enzymes were found in the mature secretory granules of alpha-cells, close to their substrate (glucagon) and their product (MG). Finally, we found NRDc only in the fractions from perfused pancreas that contain glucagon and MG after stimulation by hypoglycemia. We conclude that MGE is composed of NRDc and aminopeptidase B acting sequentially, providing a molecular basis for this uncommon regulatory process, which should be now addressed in both physiological and pathophysiological situations.
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- 2005
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48. Squash inhibitors: from structural motifs to macrocyclic knottins.
- Author
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Chiche L, Heitz A, Gelly JC, Gracy J, Chau PT, Ha PT, Hernandez JF, and Le-Nguyen D
- Subjects
- Amino Acid Sequence, Cyclization, Drug Design, Humans, Molecular Sequence Data, Protein Folding, Proteins genetics, Proteins isolation & purification, Proteins pharmacology, Serine Proteinase Inhibitors chemical synthesis, Serine Proteinase Inhibitors isolation & purification, Serine Proteinase Inhibitors pharmacology, Cucurbita chemistry, Proteins chemistry, Serine Proteinase Inhibitors chemistry
- Abstract
In this article, we will first introduce the squash inhibitor, a well established family of highly potent canonical serine proteinase inhibitors isolated from Cucurbitaceae. The squash inhibitors were among the first discovered proteins with the typical knottin fold shared by numerous peptides extracted from plants, animals and fungi. Knottins contain three knotted disulfide bridges, two of them arranged as a Cystine-Stabilized Beta-sheet motif. In contrast to cyclotides for which no natural linear homolog is known, most squash inhibitors are linear. However, Momordica cochinchinensis Trypsin Inhibitor-I and (MCoTI-I and -II), 34-residue squash inhibitors isolated from seeds of a common Cucurbitaceae from Vietnam, were recently shown to be macrocyclic. In these circular squash inhibitors, a short peptide linker connects residues that correspond to the N- and C-termini in homologous linear squash inhibitors. In this review we present the isolation, characterization, chemical synthesis, and activity of these macrocyclic knottins. The solution structure of MCoTI-II will be compared with topologically similar cyclotides, homologous linear squash inhibitors and other knottins, and potential applications of such scaffolds will be discussed.
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- 2004
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49. Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine.
- Author
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Pellissier S, Sasaki K, Le-Nguyen D, Bataille D, and Jarrousse C
- Subjects
- Animals, Eating physiology, Gastrointestinal Motility physiology, Glicentin, Intestine, Small physiology, Male, Oxyntomodulin, Rats, Rats, Wistar, Eating drug effects, Gastrointestinal Motility drug effects, Glucagon pharmacology, Glucagon-Like Peptides pharmacology, Intestine, Small drug effects, Peptide Fragments pharmacology, Protein Precursors pharmacology
- Abstract
Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33-69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three- to fourfold increase of the preprandial OXM-GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P < 0.05). In the small intestine, the duration of postprandial myoelectrical activity (50-60 min g(-1) of ingested food) was reduced by 70% (P < 0.001) on duodenum or jejunum and by 54% (P < 0.01) on ileum in OXM-treated rats. An interdigestive motility profile was settled and an acceleration of both gastric emptying and transit rate was thereafter evidenced (after T 3 h). GLIC also reduced the duration of the postprandial myoelectrical activity on duodenum and jejunum (65 and 63% respectively, P < 0.05), but was not as efficient as OXM on ileum. In pathological states such as acute adult gastroenteritis, OXM and GLIC exhibit a two- to fivefold increase in their plasma concentrations. The present findings suggest that OXM and GLIC could, in that disease, contribute to exclude pathogens, due to their joined action on gut motility.
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- 2004
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50. The KNOTTIN website and database: a new information system dedicated to the knottin scaffold.
- Author
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Gelly JC, Gracy J, Kaas Q, Le-Nguyen D, Heitz A, and Chiche L
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Animals, Computational Biology, Humans, Information Storage and Retrieval, Internet, Molecular Sequence Data, Protein Structure, Tertiary, Proteins metabolism, Structure-Activity Relationship, Terminology as Topic, Cystine chemistry, Databases, Protein, Disulfides chemistry, Proteins chemistry
- Abstract
The KNOTTIN website and database organize information about knottins or inhibitor cystine knots, small disulfide-rich proteins with a knotted topology. Thanks to their small size and high stability, knottins provide appealing scaffolds for protein engineering and drug design. Static pages present the main historical and recent results about knottin discoveries, sequences, structures, folding, functions, applications and bibliography. Database searches provide dynamically generated tabular reports or sequence alignments for knottin three-dimensional structures or sequences. BLAST/HMM searches are also available. A simple nomenclature, based on loop lengths between cysteines, is proposed and is complemented by a uniform numbering scheme. This standardization is applied to all knottin structures in the database, facilitating comparisons. Renumbered and structurally fitted knottin PDB files are available for download. The standardized numbering is used for automatic drawing of two-dimensional Colliers de Perles. The KNOTTIN website and database are available at http://knottin.cbs.cnrs.fr and http://knottin.com.
- Published
- 2004
- Full Text
- View/download PDF
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