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16 results on '"Christophe Piesse"'

1. Characterization of a New Immunosuppressive and Antimicrobial Peptide, DRS-DA2, Isolated from the Mexican Frog, Pachymedusa dacnicolor

Author

Claire Lacombe, Estefania Aleman-Navaro, Thierry Drujon, Veronica Martinez-Osorio, Emmanuelle Sachon, Erika Melchy-Pérez, Ludovic Carlier, Lorena Elizabeth Fajardo Brigido, Yannick Fleury, Christophe Piesse, Guadalupe Gutiérrez-Escobedo, Alejandro De las Peñas, Irene Castaño, Florie Desriac, Jose Luis Beristain-Hernandez, Christophe Combadiere, Yvonne Rosenstein, and Constance Auvynet

Subjects
Pathology, RB1-214
Abstract

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections.

Published
2024
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2. Reverse Immunology Approach to Define a New HIV-gp41-Neutralizing Epitope

Author

Karim Dorgham, Nicolas Pietrancosta, Amel Affoune, Olivier Lucar, Tahar Bouceba, Solenne Chardonnet, Cedric Pionneau, Christophe Piesse, Delphine Sterlin, Pablo Guardado-Calvo, Philippe Karoyan, Patrice Debré, Guy Gorochov, and Vincent Vieillard

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

The design of immunogens susceptible to elicit potent and broadly neutralizing antibodies against the human immunodeficiency virus type 1 (HIV-1) remains a veritable challenge in the course of vaccine development. Viral envelope proteins adopt different conformational states during the entry process, allowing the presentation of transient neutralizing epitopes. We focused on the highly conserved 3S motif of gp41, which is exposed to the surface envelope in its trimeric prefusion state. Vaccination with a W614A-modified 3S peptide induces in animals neutralizing anti-HIV-1 antibodies among which we selected clone F8. We used F8 as bait to select for W614A-3S phage-peptide mimics. Binding and molecular docking studies revealed that F8 interacts similarly with W614A-3S and a Mim_F8-1 mimotope, despite their lack of sequence homology, suggesting structural mimicry. Finally, vaccination of mice with the purified Mim_F8-1 phage elicited HIV-1-neutralizing antibodies that bound to the cognate W614A-3S motif. Collectively, our findings provide new insights into the molecular design of immunogens to elicit antibodies with neutralizing properties.

Published
2019
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3. Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin.

Author

Sébastien Cardon, Emmanuelle Sachon, Ludovic Carlier, Thierry Drujon, Astrid Walrant, Estefanía Alemán-Navarro, Verónica Martínez-Osorio, Dominique Guianvarc'h, Sandrine Sagan, Yannick Fleury, Rodrigue Marquant, Christophe Piesse, Yvonne Rosenstein, Constance Auvynet, and Claire Lacombe

Subjects
Medicine, Science
Abstract

The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an α-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan.

Published
2018
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4. Engineering of Antimicrobial Surfaces by Using Temporin Analogs to Tune the Biocidal/antiadhesive Effect

Author

Pierre-Carl Oger, Christophe Piesse, Ali Ladram, and Vincent Humblot

Subjects
temporin-SHa, SHa analogs, antimicrobial peptides, gold surface functionalization, antibacterial/antiadhesive activity, Organic chemistry, QD241-441
Abstract

Proliferation of resistant bacteria on biomaterials is a major problem leading to nosocomial infections. Due to their broad-spectrum activity and their ability to disrupt bacterial membranes through a rapid membranolytic mechanism, antimicrobial peptides (AMPs) are less susceptible to the development of bacterial resistance and therefore represent good candidates for surface coating strategies to prevent biofilm formation. In this study, we report on the covalent immobilization of temporin-SHa, a small hydrophobic and low cationic antimicrobial peptide exhibiting broad-spectrum activity, and (SHa) analogs on modified gold surfaces. Several analogs derived from SHa with either a carboxamidated ([K3]SHa, d-[K3]SHa) or a carboxylated C-terminus ([K3]SHa-COOH) were used to achieve peptide grafting on gold surfaces modified by a thiolated self-assembled monolayer (SAM). Surface functionalization was characterized by polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoemission spectroscopy (XPS). The antibacterial properties of the temporin-functionalized surfaces were tested against the Gram-positive Listeria ivanovii. Direct visualization of the peptide effects on the bacterial membrane was investigated by scanning electron microscopy equipped with a field emission gun (SEM-FEG). All active temporin analogs were successfully grafted and display significant antibacterial activity (from 80 to 90% killing efficiency) in addition to a 2-fold decrease of bacterial adhesion when all d-SHa analogs were used.

Published
2019
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5. Identification of the Single Immunodominant Region of the Native Human CC Chemokine Receptor 6 Recognized by Mouse Monoclonal Antibodies.

Author

Karim Dorgham, Cécile Dejou, Christophe Piesse, Guy Gorochov, Jérôme Pène, and Hans Yssel

Subjects
Medicine, Science
Abstract

Chemokines and their receptors play an important role in cell trafficking and recruitment. The CCR6 chemokine receptor, selectively expressed on leukocyte populations, has been shown to play a deleterious role in the pathogenesis of various chronic inflammatory diseases and, as such, may constitute a prime target in the development of immunotherapeutic treatment. However, to date no neutralizing mouse monoclonal antibodies (mAbs) specific for this chemokine receptor have been reported, whereas information on small molecules capable of interfering with the interaction of CCR6 and its ligands is scant. Here, we report the failure to generate neutralizing mouse mAbs specific for human (hu)CCR6. Immunization of mice with peptides mimicking extracellular domains, potentially involved in CCR6 function, failed to induce Abs reactive with the native receptor. Although the use of NIH-3T3 cells expressing huCCR6 resulted in the isolation of mAbs specific for this receptor, they were not able to block the interaction between huCCR6 and huCCL20. Investigation of the anti-huCCR6 mAbs generated in the present study, as well as those commercially available, show that all mAbs invariably recognize a unique, non-neutralizing, immunodominant region in the first part of its N-terminal domain. Together, these results indicate that the generation of potential neutralizing anti-huCCR6 mAbs in the mouse is unlikely to succeed and that alternative techniques, such as the use of other animal species for immunization, might constitute a better approach to generate such a potentially therapeutic tool for the treatment of inflammatory disease.

Published
2016
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6. Structure, antimicrobial activities and mode of interaction with membranes of novel [corrected] phylloseptins from the painted-belly leaf frog, Phyllomedusa sauvagii.

Author

Zahid Raja, Sonia André, Christophe Piesse, Denis Sereno, Pierre Nicolas, Thierry Foulon, Bruno Oury, and Ali Ladram

Subjects
Medicine, Science
Abstract

Transcriptomic and peptidomic analysis of skin secretions from the Painted-belly leaf frog Phyllomedusa sauvagii led to the identification of 5 novel phylloseptins (PLS-S2 to -S6) and also of phylloseptin-1 (PSN-1, here renamed PLS-S1), the only member of this family previously isolated in this frog. Synthesis and characterization of these phylloseptins revealed differences in their antimicrobial activities. PLS-S1, -S2, and -S4 (79-95% amino acid sequence identity; net charge = +2) were highly potent and cidal against Gram-positive bacteria, including multidrug resistant S. aureus strains, and killed the promastigote stage of Leishmania infantum, L. braziliensis and L. major. By contrast, PLS-S3 (95% amino acid identity with PLS-S2; net charge = +1) and -S5 (net charge = +2) were found to be almost inactive against bacteria and protozoa. PLS-S6 was not studied as this peptide was closely related to PLS-S1. Differential scanning calorimetry on anionic and zwitterionic multilamellar vesicles combined with circular dichroism spectroscopy and membrane permeabilization assays on bacterial cells indicated that PLS-S1, -S2, and -S4 are structured in an amphipathic α-helix that disrupts the acyl chain packing of anionic lipid bilayers. As a result, regions of two coexisting phases could be formed, one phase rich in peptide and the other lipid-rich. After reaching a threshold peptide concentration, the disruption of lipid packing within the bilayer may lead to local cracks and disintegration of the microbial membrane. Differences in the net charge, α-helical folding propensity, and/or degree of amphipathicity between PLS-S1, -S2 and -S4, and between PLS-S3 and -S5 appear to be responsible for their marked differences in their antimicrobial activities. In addition to the detailed characterization of novel phylloseptins from P. sauvagii, our study provides additional data on the previously isolated PLS-S1 and on the mechanism of action of phylloseptins.

Published
2013
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8. Development and Characterization of Innovative Multidrug Nanoformulation for Cardiac Therapy

Author

Amandine Gendron, Séverine Domenichini, Sandrine Zanna, Frédéric Gobeaux, Christophe Piesse, Didier Desmaële, Mariana Varna, Institut Galien Paris-Saclay (IGPS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
cytotoxicity, [CHIM]Chemical Sciences, therapeutic peptide, nanoparticles, General Materials Science, antioxidant capacity, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, bioconjugate
Abstract

International audience; For several decades, various peptides have been under investigation to prevent ischemia/reperfusion (I/R) injury, including cyclosporin A (CsA) and Elamipretide. Therapeutic peptides are currently gaining momentum as they have many advantages over small molecules, such as better selectivity and lower toxicity. However, their rapid degradation in the bloodstream is a major drawback that limits their clinical use, due to their low concentration at the site of action. To overcome these limitations, we have developed new bioconjugates of Elamipretide by covalent coupling with polyisoprenoid lipids, such as squalenic acid or solanesol, embedding self-assembling ability. The resulting bioconjugates were co-nanoprecipitated with CsA squalene bioconjugate to form Elamipretide decorated nanoparticles (NPs). The subsequent composite NPs were characterized with respect to mean diameter, zeta potential, and surface composition by Dynamic Light Scattering (DLS), Cryogenic Transmission Electron Microscopy (CryoTEM) and X-ray Photoelectron Spectrometry (XPS). Further, these multidrug NPs were found to have less than 20% cytotoxicity on two cardiac cell lines even at high concentrations, while maintaining an antioxidant capacity. These multidrug NPs could be considered for further investigations as an approach to target two important pathways involved in the development of cardiac I/R lesions.

Published
2023
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9. The effects of curcumin, mangiferin, resveratrol and other natural plant products on aminopeptidase B activity

Author

Cécile Darmon, Mouna Mahbouli, Thanos Ghelis, Sandrine Cadel, Thierry Foulon, Alexandre Désert, Christophe Piesse, René Lafont, Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Curcumin, Coumaric Acids, Xanthones, [SDV]Life Sciences [q-bio], Biophysics, Resveratrol, Aminopeptidases, Biochemistry, Aminopeptidase, Leukotriene-A4 hydrolase, 03 medical and health sciences, chemistry.chemical_compound, Aminopeptidase B, 0302 clinical medicine, Leukotriene A4 hydrolase, Coumarins, Nardilysin, Animals, Glucose homeostasis, Protease Inhibitors, Mangiferin, Molecular Biology, Biological Products, Cell Biology, Recombinant Proteins, Rats, Molecular Docking Simulation, [SDV] Life Sciences [q-bio], Kinetics, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis
Abstract

International audience; Aminopeptidase B (Ap-B) is a Zn2+-aminopeptidase of the M1 family which is implicated, in conjunction with the nardilysin endoprotease, in the generation of miniglucagon, a peptide involved in the maintenance of glucose homeostasis. Other in vivo physiological roles have been established for this vertebrate enzyme, such as the processing of Arg-extended forms of human insulin and cholecystokinin 9 and the degradation of viral epitopes in the cytoplasm. Among M1 family members, Ap-B is phylogenetically close to leukotriene A4 hydrolase (LTA4H), a bi-functional aminopeptidase also able to transform LTA4 in LTB4 (a lipid mediator of inflammation). As the activities of LTA4H are reported to be inhibited by resveratrol, a polyphenolic molecule from red wine, the effect of this molecule was investigated on the Ap-B activity. Several other active phenolic compounds produced in plants were also tested. Among them, curcumin and mangiferin are the most effective inhibitors. Dixon analysis indicates that curcumin is a non-competitive inhibitor with a Ki value of 46 μmol.L−1. Dixon and Lineweaver-Burk representations with mangiferin show a mixed non-competitive inhibition with Ki’ and Ki values of 194 μmol.L−1 and 105 μmol.L−1, respectively. At 200 μmol.L−1, no significant effect was observed with caffeic, chlorogenic, ferulic, salicylic and sinapic acids as well as with resveratrol. Analyses on the 3D-structure of LTA4H with resveratrol (pdb: 3FTS) and the Ap-B 3D-model allow hypothesis to explain theses results.

Published
2019
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10. Engineering of Antimicrobial Surfaces by Using Temporin Analogs to Tune the Biocidal/antiadhesive Effect

Author

Ali Ladram, Pierre-Carl Oger, Vincent Humblot, Christophe Piesse, Laboratoire de Réactivité de Surface (LRS), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Listeria, Surface Properties, Antimicrobial peptides, Pharmaceutical Science, Peptide, 02 engineering and technology, antibacterial/antiadhesive activity, Bacterial Adhesion, Article, Analytical Chemistry, lcsh:QD241-441, 03 medical and health sciences, antimicrobial peptides, Anti-Infective Agents, lcsh:Organic chemistry, stomatognathic system, Drug Discovery, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Sulfhydryl Compounds, Physical and Theoretical Chemistry, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Chemistry, Organic Chemistry, Proteins, Drug Resistance, Microbial, gold surface functionalization, 021001 nanoscience & nanotechnology, Antimicrobial, Combinatorial chemistry, Temporin, Surface coating, Membrane, Chemistry (miscellaneous), SHa analogs, Biofilms, Molecular Medicine, Surface modification, Gold, 0210 nano-technology, Antibacterial activity, Hydrophobic and Hydrophilic Interactions, Antimicrobial Cationic Peptides, temporin-SHa
Abstract

Proliferation of resistant bacteria on biomaterials is a major problem leading to nosocomial infections. Due to their broad-spectrum activity and their ability to disrupt bacterial membranes through a rapid membranolytic mechanism, antimicrobial peptides (AMPs) are less susceptible to the development of bacterial resistance and therefore represent good candidates for surface coating strategies to prevent biofilm formation. In this study, we report on the covalent immobilization of temporin-SHa, a small hydrophobic and low cationic antimicrobial peptide exhibiting broad-spectrum activity, and (SHa) analogs on modified gold surfaces. Several analogs derived from SHa with either a carboxamidated ([K3]SHa, d-[K3]SHa) or a carboxylated C-terminus ([K3]SHa-COOH) were used to achieve peptide grafting on gold surfaces modified by a thiolated self-assembled monolayer (SAM). Surface functionalization was characterized by polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoemission spectroscopy (XPS). The antibacterial properties of the temporin-functionalized surfaces were tested against the Gram-positive Listeria ivanovii. Direct visualization of the peptide effects on the bacterial membrane was investigated by scanning electron microscopy equipped with a field emission gun (SEM-FEG). All active temporin analogs were successfully grafted and display significant antibacterial activity (from 80 to 90% killing efficiency) in addition to a 2-fold decrease of bacterial adhesion when all d-SHa analogs were used.

Published
2019
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11. Reverse Immunology Approach to Define a New HIV-gp41-Neutralizing Epitope

Author

Pablo Guardado-Calvo, Vincent Vieillard, Patrice Debré, Delphine Sterlin, Guy Gorochov, Nicolas Pietrancosta, Tahar Bouceba, Christophe Piesse, Karim Dorgham, Solenne Chardonnet, Amel Affoune, Cédric Pionneau, Olivier Lucar, Philippe Karoyan, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Ingénierie des protéines, PCR, Interaction Moléculaires [IBPS] (IBPS-IPIM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Virologie Structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Sorbonne Université and the Institut National de la Santé et de la Recherche Médicale (INSERM)., Centre d'Immunologie et des Maladies Infectieuses (CIMI), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Sorbonne Université and the Institut National de la Santé et de la Recherche Médicale (INSERM). The authors acknowledge Delphine Lucas from Minka Therapeutics and Julien Puech and Noemi Asfogo, both students of the CIMI-Paris, for their technical assistance., Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dorgham, Karim, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Models, Molecular, lcsh:Immunologic diseases. Allergy, Article Subject, Immunology, Human immunodeficiency virus (HIV), Peptide, HIV Antibodies, Biology, Gp41, medicine.disease_cause, Epitopes, Mice, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, 0302 clinical medicine, Viral envelope, Neutralization Tests, medicine, Animals, Immunology and Allergy, Bacteriophages, 030304 developmental biology, chemistry.chemical_classification, Mice, Inbred BALB C, 0303 health sciences, Mimotope, Antibodies, Monoclonal, General Medicine, Antibodies, Neutralizing, Virology, HIV Envelope Protein gp41, 3. Good health, Neutralizing epitope, Molecular Docking Simulation, Vaccination, chemistry, 030220 oncology & carcinogenesis, HIV-1, biology.protein, Antibody, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Peptides, lcsh:RC581-607, Epitope Mapping, Research Article, Protein Binding
Abstract

International audience; The design of immunogens susceptible to elicit potent and broadly neutralizing antibodies against the human immunodeficiency virus type 1 (HIV-1) remains a veritable challenge in the course of vaccine development. Viral envelope proteins adopt different conformational states during the entry process, allowing the presentation of transient neutralizing epitopes. We focused on the highly conserved 3S motif of gp41, which is exposed to the surface envelope in its trimeric prefusion state. Vaccination with a W614A-modified 3S peptide induces in animals neutralizing anti-HIV-1 antibodies among which we selected clone F8. We used F8 as bait to select for W614A-3S phage-peptide mimics. Binding and molecular docking studies revealed that F8 interacts similarly with W614A-3S and a Mim_F8-1 mimotope, despite their lack of sequence homology, suggesting structural mimicry. Finally, vaccination of mice with the purified Mim_F8-1 phage elicited HIV-1-neutralizing antibodies that bound to the cognate W614A-3S motif. Collectively, our findings provide new insights into the molecular design of immunogens to elicit antibodies with neutralizing properties.

Published
2019
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12. Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long membrane-damaging peptide

Author

Ali Ladram, Pierre Nicolas, Bruno Oury, Christophe Piesse, Elodie Gazanion, Thierry Foulon, Denis Sereno, Zahid Raja, Feten Abbassi, Ingénierie des protéines, PCR, Interaction Moléculaires [IBPS] (IBPS-IPIM), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE), UPMC, Agence Nationale pour la Recherche (ANR-Prob DOM), DVS/AIRD (Direction de la Valorisation au Sud/Agence Inter-etablissements de Recherche pour le Developpement), and French Ministere de l'Enseignement Superieur et de la Recherche [ED 387]

Subjects
Trypanosoma, Ranidae, Stereochemistry, Antiparasitic, medicine.drug_class, [SDV]Life Sciences [q-bio], Membrane interactionpermeabilization, Lipid Bilayers, Molecular Sequence Data, Antimicrobial peptides, Peptide, Circular dichroism, Biology, Gram-Positive Bacteria, Antiparasitic activity, Biochemistry, Amphibian Proteins, Cell Line, Inhibitory Concentration 50, Anti-Infective Agents, Gram-Negative Bacteria, medicine, Animals, Humans, Amino Acid Sequence, Membrane interaction/permeabilization, Leishmania infantum, Amastigote, Peptide sequence, Phospholipids, Solid-Phase Synthesis Techniques, Skin, chemistry.chemical_classification, Circular Dichroism, Macrophages, Proteins, Temporin-SH, General Medicine, Amphibian, Antimicrobial, Temporin, Mechanism of action, chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, medicine.symptom, Antimicrobial peptide, Antimicrobial Cationic Peptides
Abstract

International audience; Temporins are a family of short antimicrobial peptides (8-17 residues) that mostly show potent activity against Gram-positive bacteria. Herein, we demonstrate that temporin-SHd, a 17-residue peptide with a net charge of +2 (FLPAALAGIGGILGKLF(amide)) expressed a broad spectrum of antimicrobial activity. This peptide displayed potent antibacterial activities against Gram-negative and Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus strains, as well as antiparasitic activity against promastigote and the intracellular stage (amastigote) of Leishmania infantum, at concentration not toxic for the macrophages. Temporin-SHd that is structured in a non-amphipathic alpha-helix in anionic membrane-mimetic environments, strongly and selectively perturbs anionic bilayer membranes by interacting with the polar head groups and acyl region of the phospholipids, with formation of regions of two coexisting phases: one phase rich in peptide and the other lipid-rich. The disruption of lipid packing within the bilayer may lead to the formation of transient pores and membrane permeation/disruption once a threshold peptide accumulation is reached. To our knowledge, Temporin-SHd represents the first known 17-residue long temporin expressing such broad spectrum of antimicrobial activity including members of the trypanosomatidae family. Additionally, since only a few shorter members (13 residues) of the temporin family are known to display antileishmanial activity (temporins-TA, -TB and -SHa), SHd is an interesting tool to analyze the antiparasitic mechanism of action of temporins.

Published
2013
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13. Identification of the Single Immunodominant Region of the Native Human CC Chemokine Receptor 6 Recognized by Mouse Monoclonal Antibodies

Author

Guy Gorochov, Hans Yssel, Jérôme Pène, Cécile Dejou, Christophe Piesse, Karim Dorgham, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ingénierie des protéines, PCR, Interaction Moléculaires [IBPS] (IBPS-IPIM), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and HAL-UPMC, Gestionnaire

Subjects
0301 basic medicine, Chemokine, Physiology, Cell Lines, lcsh:Medicine, C-C chemokine receptor type 6, Immune Receptors, Biochemistry, Pathogenesis, Mice, Chemokine receptor, Spectrum Analysis Techniques, Immune Physiology, Medicine and Health Sciences, Enzyme-Linked Immunoassays, lcsh:Science, Receptor, Mice, Inbred BALB C, Immune System Proteins, Multidisciplinary, biology, Chemotaxis, Antibodies, Monoclonal, Animal Models, Flow Cytometry, Recombinant Proteins, 3. Good health, Cell Motility, Spectrophotometry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cytophotometry, Biological Cultures, Chemokines, Research Article, Signal Transduction, Receptors, CCR6, Cell Binding, Cell Physiology, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Immunology, Mouse Models, Research and Analysis Methods, Monoclonal antibody, Antibodies, Cell Line, 03 medical and health sciences, Model Organisms, medicine, Animals, Humans, Immunoassays, Chemokine CCL20, Hybridomas, Immunodominant Epitopes, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, Antibodies, Neutralizing, 030104 developmental biology, Immunization, NIH 3T3 Cells, Immunologic Techniques, biology.protein, lcsh:Q, Binding Sites, Antibody, CC chemokine receptors
Abstract

International audience; Chemokines and their receptors play an important role in cell trafficking and recruitment. The CCR6 chemokine receptor, selectively expressed on leukocyte populations, has been shown to play a deleterious role in the pathogenesis of various chronic inflammatory diseases and, as such, may constitute a prime target in the development of immunotherapeutic treatment. However, to date no neutralizing mouse monoclonal antibodies (mAbs) specific for this chemokine receptor have been reported, whereas information on small molecules capable of interfering with the interaction of CCR6 and its ligands is scant. Here, we report the failure to generate neutralizing mouse mAbs specific for human (hu)CCR6. Immunization of mice with peptides mimicking extracellular domains, potentially involved in CCR6 function, failed to induce Abs reactive with the native receptor. Although the use of NIH-3T3 cells expressing huCCR6 resulted in the isolation of mAbs specific for this receptor, they were not able to block the interaction between huCCR6 and huCCL20. Investigation of the anti-huCCR6 mAbs generated in the present study, as well as those commercially available , show that all mAbs invariably recognize a unique, non-neutralizing, immunodominant region in the first part of its N-terminal domain. Together, these results indicate that the generation of potential neutralizing anti-huCCR6 mAbs in the mouse is unlikely to succeed and that alternative techniques, such as the use of other animal species for immunization, might constitute a better approach to generate such a potentially therapeutic tool for the treatment of inflammatory disease.

Published
2016
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14. Structure, Antimicrobial Activities and Mode of Interaction with Membranes of Bovel Phylloseptins from the Painted-Belly Leaf Frog, Phyllomedusa sauvagii

Author

Zahid Raja, Sonia André, Christophe Piesse, Denis Sereno, Pierre Nicolas, Thierry Foulon, Bruno Oury, Ali Ladram, Ingénierie des protéines, PCR, Interaction Moléculaires [IBPS] (IBPS-IPIM), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE)

Subjects
0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary, Science, [SDV]Life Sciences [q-bio], Correction, Medicine, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience; no abstract

Published
2013
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15. Human aminopeptidase B (rnpep) on chromosome 1q32.2: complementary DNA, genomic structure and expression

Author

Christophe Piesse, Paul Cohen, Cécile Gouzy, Michel Lacasa, Sandrine Cadel, Martin Tymms, Emirena Garrafa, and Thierry Foulon

Subjects
Male, DNA, Complementary, Molecular Sequence Data, Gene Expression, HL-60 Cells, Aminopeptidases, Aminopeptidase B, Exon, Mice, Complementary DNA, Genetics, Tumor Cells, Cultured, Translocase, Animals, Humans, Amino Acid Sequence, RNA, Messenger, Promoter Regions, Genetic, Gene, Transcription factor, Metalloexopeptidase, Epoxide Hydrolases, Messenger RNA, biology, Base Sequence, Sequence Homology, Amino Acid, General Medicine, Sequence Analysis, DNA, Molecular biology, Rats, Genes, Chromosomes, Human, Pair 1, biology.protein, Female, Caco-2 Cells, K562 Cells, Sequence Alignment
Abstract

Aminopeptidase B (APB) is a Zn 2+ -metalloexopeptidase, which selectively removes Arg and/or Lys residues from the N-terminus of several peptide substrates. Several data strongly support the hypothesis that this enzyme could participate in the final stages of precursor processing mechanisms and/or in particular inflammatory processes and tumor developments. Therefore, we have cloned the complementary DNA encoding the human APB, a 658-residues protein, containing the canonical ‘HEXXH(X 18 ) E’, a signature allowing its classification in the M1 family of metallopeptidases. The genomic structure of the human APB gene ( rnpep ; 1q32.1–q32.2) was also determined. rnpep is bracketed by pre-protein translocase of the inner mitochondrial membrane gene and ETS family transcription factor ELF3 gene. It spans more than 24 kbp and contains 11 exons ranging from 109 to 574 bp. Finally, expression of the human APB messenger RNA (mRNA) was investigated using a pre-made dot-blot. This mRNA seems to be ubiquitous although its expression level varies depending of the cells or tissues considered.

Published
2002

16. Structure, Antimicrobial Activities and Mode of Interaction with Membranes of Bovel Phylloseptins from the Painted-Belly Leaf Frog, Phyllomedusa sauvagii

Author

Pierre Nicolas, Thierry Foulon, Ali Ladram, Bruno Oury, Zahid Raja, Christophe Piesse, Sonia André, Denis Sereno, Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des protéines, PCR, Interaction Moléculaires [IBPS] (IBPS-IPIM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), UPMC, Agence Nationale pour la Recherche (ANR-Prob DOM), DVS/AIRD (Direction de la Valorisation au Sud/Agence Inter-etablissements de Recherche pour le Developpement), French Ministere de l'Enseignement Superieur et de la Recherche, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Proteomics, Lipopolysaccharides, Models, Molecular, Circular dichroism, Cell Membrane Permeability, Protein Conformation, [SDV]Life Sciences [q-bio], Peptide, Biochemistry, 0302 clinical medicine, Protein structure, Cloning, Molecular, Leishmania infantum, Lipid bilayer, Peptide sequence, Skin, chemistry.chemical_classification, Chromatography, 0303 health sciences, Spectrometric Identification of Proteins, Multidisciplinary, biology, Chemistry, Vesicle, Amino acid, Phyllomedusa sauvagii, Medicine, Anura, Research Article, Protein Binding, Protein Structure, Staphylococcus aureus, Science, Molecular Sequence Data, Biophysics, Microbial Sensitivity Tests, Amphibian Proteins, Inhibitory Concentration 50, 03 medical and health sciences, Defense Proteins, Escherichia coli, Synthetic Peptide, Animals, Amino Acid Sequence, Protein Interactions, Biology, 030304 developmental biology, Reversed-Phase Chromatography, Membranes, Base Sequence, Dose-Response Relationship, Drug, Proteins, biology.organism_classification, Kinetics, 030217 neurology & neurosurgery, Antimicrobial Cationic Peptides
Abstract

International audience; Transcriptomic and peptidomic analysis of skin secretions from the Painted-belly leaf frog Phyllomedusa sauvagii led to the identification of 5 novel phylloseptins (PLS-S2 to -S6) and also of phylloseptin-1 (PSN-1, here renamed PLS-S1), the only member of this family previously isolated in this frog. Synthesis and characterization of these phylloseptins revealed differences in their antimicrobial activities. PLS-S1, -S2, and -S4 (79-95% amino acid sequence identity; net charge = +2) were highly potent and cidal against Gram-positive bacteria, including multidrug resistant S. aureus strains, and killed the promastigote stage of Leishmania infantum, L. braziliensis and L. major. By contrast, PLS-S3 (95% amino acid identity with PLS-S2; net charge = +1) and -S5 (net charge = +2) were found to be almost inactive against bacteria and protozoa. PLS-S6 was not studied as this peptide was closely related to PLS-S1. Differential scanning calorimetry on anionic and zwitterionic multilamellar vesicles combined with circular dichroism spectroscopy and membrane permeabilization assays on bacterial cells indicated that PLS-S1, -S2, and -S4 are structured in an amphipathic a-helix that disrupts the acyl chain packing of anionic lipid bilayers. As a result, regions of two coexisting phases could be formed, one phase rich in peptide and the other lipid-rich. After reaching a threshold peptide concentration, the disruption of lipid packing within the bilayer may lead to local cracks and disintegration of the microbial membrane. Differences in the net charge, a-helical folding propensity, and/or degree of amphipathicity between PLS-S1, -S2 and -S4, and between PLS-S3 and -S5 appear to be responsible for their marked differences in their antimicrobial activities. In addition to the detailed characterization of novel phylloseptins from P. sauvagii, our study provides additional data on the previously isolated PLS-S1 and on the mechanism of action of phylloseptins.

Published
2013
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