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The achiral tetrapeptide monohydrate N‐(benzyloxycarbonyl)glycyl‐α‐aminoisobutyrylglycyl‐α‐aminoisobutyric acid monohydrate, Z–Gly–Aib–Gly–Aib–OH·H2O (Z is benzyloxycarbonyl, Aib is α‐aminoisobutyric acid and Gly is glycine) or C20H28N4O7·H2O, exhibits two conformations related by the symmetry operation of an inversion centre. It adopts only one of two possible intramolecular hydrogen bonds in a type I (and I′) β‐turn and forms a maximum of intermolecular hydrogen bonds partly mediated by water. The space group, the molecular structure and the crystal packing differ from two already described (Gly–Aib)2 peptides which vary only in the protecting groups. This structure confirms the high structural flexibility of Gly–Aib peptides and points to a strong relationship between intermolecular hydrogen bonding and crystal quality and size. [ABSTRACT FROM AUTHOR]

β-aminoisobutyric acid (BAIBA) has been studied in isolation conditions: in the gas phase and trapped into a cryogenic N2 matrix. A solid sample of the compound was vaporized by laser ablation and investigated through their rotational spectra in a supersonic expansion using two different spectroscopic techniques: broadband chirped pulse Fourier transform microwave spectroscopy and conventional molecular beam Fourier transform microwave spectroscopy. Four conformers with structures of two types could be successfully identified by comparison of the experimental rotational and 14N nuclear quadruple coupling constants with those predicted theoretically: type A, bearing an OH...N intramolecular hydrogen bond and its carboxylic group in the trans geometry (H-O-C=O dihedral ∼180°), and type B, having an NH...O bond and the cis arrangement of the carboxylic group. These two types of conformers could also be trapped from the gas phase into a cryogenic N2 matrix and probed by Fourier transform infrared (IR) spectroscopy. In situ irradiation of BAIBA isolated in N2 matrix of type B conformers using near-IR radiation tuned at the frequency of the O-H stretching 1st overtone (∼6930 cm-1) of these forms allowed to selectively convert them into type A conformers and into a new type of conformers of higher energy (type D) bearing an NH...O=C bond and a O-H 'free' trans carboxylic group. [ABSTRACT FROM AUTHOR]

It is not clear whether inhibition of p70 ribosomal S6 kinase 1 (S6K1) is neuroprotective in cerebral ischemia-reperfusion. Decreasing blood-brain barrier (BBB) disruption has been associated with a better neuronal outcome in cerebral ischemia. We hypothesized that inhibition of S6K1 would decrease BBB disruption and infarct size in the early stage of cerebral ischemia-reperfusion. Middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. 75 mg/kg of PF-4708671, an S6K1 inhibitor, was administered intraperitoneally 15 min after MCAO. After 1 h of MCAO and 2 h of reperfusion, the transfer coefficient (K i) of 14C-α-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to assess the degree of BBB disruption. At the same time point, phosphorylated Rictor (pT1135) and the infarct size were measured to evaluate S6K1 activity. In the PF-4708671 treated rats, the K i of the ischemic-reperfused cortex was lower than the untreated rats (−22%, P < 0.05) and the volume of dextran distribution was significantly lower in most brain regions. With PF-4708671, a significant decrease in pT1135 Rictor was observed and the percentage of cortical infarct out of total cortical area was decreased (11.6 ± 2.0% vs 7.2 ± 1.1%, P < 0.0001). Our data demonstrate that PF-4708671 decreased the size of the cortical infarct in the ischemic-reperfused cortex with a decrease in BBB disruption suggesting that inhibition of S6K1 may induce neuronal survival in early cerebral ischemia-reperfusion and that a decrease of BBB disruption could be one of the contributing factors. [ABSTRACT FROM AUTHOR]

Abstract Fabrication of amine-containing membranes for removal of H 2 S and CO 2 from reformate gas for hydrogen purification for fuel cells was scaled up by using a continuous roll-to-roll membrane fabrication machine. The membrane contained aminoisobutyric acid-potassium salt as the mobile carrier and polyvinylamine as the fixed-site carrier for facilitated transport of acid gases in crosslinked polyvinylalcohol as the membrane matrix. Three key variables controlling the membrane selective layer thickness, i.e., the coating solution, substrate web coating speed, and coating knife gap setting, were identified and studied. Membranes in 14 in. in width and > 150 feet in length were fabricated with a uniform selective layer thickness of around 15 µm. The scale-up membranes demonstrated similar performances as the lab-scale membranes with a CO 2 permeance of more than 200 GPU, CO 2 /H 2 selectivity of greater than 200, and H 2 S/H 2 selectivity of higher than 600. The scale-up membranes were used for the fabrication of prototype spiral-wound membrane modules for a field test with autothermal reformate gas as the feed gas. The modeling and optimization of the hydrogen purification process were performed to identify the optimum test conditions for the spiral-wound membrane modules. The modeling results showed that the membrane removed H 2 S to less than 10 ppm and CO 2 to < 1% in the hydrogen product with more than 99% of H 2 recovery for the case of using a wet sweep gas with 40% moisture. The field test results showed that the H 2 S and CO 2 concentrations were about 4–10 ppm and < 3%, respectively, in the hydrogen product on a wet basis and that the agreement between the modeling results and the test results was reasonably good. Highlights • Fabrication of amine-containing CO 2 -selective membrane for H 2 S removal was scaled up. • Scale-up membranes were tested with both simulated and actual reformate gases as the feed gases. • Modeling and process optimization were performed to identify the optimum module test conditions. • Good membrane performance was obtained in agreement with the modeling results. • Field test results have shown the potential for H 2 S removal in fuel cell application. [ABSTRACT FROM AUTHOR]

The simplest non‐proteinogenic amino acid α‐aminoisobutyric acid (Aib), an analogue of glycine and alanine, has been vaporized by laser ablation and probed by high‐resolution Fourier transform microwave spectroscopic techniques. Comparison of the experimental rotational and 14N nuclear quadrupole constants with that predicted ab initio has allowed the identification of three conformers of Aib exhibiting three types of hydrogen‐bond interactions I (NH⋅⋅⋅O=C, cis‐COOH), II (OH⋅⋅⋅N, trans‐COOH), and III (N−H⋅⋅⋅O−H, cis‐COOH) within the amino acid backbone. The observation of conformer III, not detected previously for related proteinogenic amino acids with a nonpolar side chain in a supersonic expansion, indicates that the presence of the methyl groups should restrict the conformational relaxation from conformer Aib‐III to Aib‐I. For conformer Aib‐II, the rotational spectra of the 13C isotopomers reveal a tunneling motion arising from the two equivalent methyl groups in the molecule. The observation of a single spectrum at the midpoint between those predicted for the two 13C of the methyl groups has been explained by considering a double‐minimum potential function with a low‐energy interconversion barrier for a large amplitude internal motion. This singular fact has been corroborated by the anomalous centrifugal distortion effects determined in conformer Aib‐II. Maxing and relaxing: Three conformers of the non‐proteinogenic amino acid α‐aminoisobutyric acid (Aib) have been revealed in a supersonic expansion by laser ablation and high‐resolution Fourier transform microwave techniques. For the first time, a conformer showing the N−H⋅⋅⋅O−H intramolecular interaction has been detected and characterized (see figure). This study deepens our understanding of the relaxation process. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A novel HILIC method for the determination of 2-aminoisobutyric acid in enzalutamide drug was presented. • The postcolumn conditions such as temperature and reagent flow rate were studied. • The proposed HILIC method was validated in accordance with ICH guidelines. Abstract A rapid procedure for the determination of 2-aminoisobutyric acid in enzalutamide bulk drug substance based on hydrophilic interaction chromatography with fluorescence detection was developed. Fluorescence detection after postcolumn derivatization with o -phthaldialdehyde/2-mercaptoethanol was carried out at excitation and emission wavelength of 345 nm and 450 nm, respectively. The postcolumn reaction conditions such as reaction temperature, mobile phase and derivatization reagent flow rate and the reagents concentrations were studied and optimized due to steric hindrance of amino group of 2-aminoisobutyric acid. The derivatization reaction was applied for the hydrophilic interaction chromatography method which was based on COSMOSIL HILIC column with a mobile phase consisting of a mixture of 25 mmol/L acetic acid adjusted to pH 5.5 (using 1 mol/L potassium hydroxide) and acetonitrile using an isocratic elution (28:72, ν/ν). The benefit of the reported approach consists in a simple sample pretreatment and a quick and sensitive hydrophilic interaction chromatography method. The developed method was validated in terms of linearity, limit of detection, limit of quantification, accuracy, precision and selectivity according to the International Conference on Harmonisation guidelines. The developed method was demonstrated to be applied for the analysis of 2-AIBA in routine quality control evaluation of commercial samples of enzalutamide bulk drug substance. [ABSTRACT FROM AUTHOR]

Objective: Initial studies on the use of non-physiological amino acids (NPAAs) to block the accretion of Phe in the brain of Pahenu2−/− mice revealed that 2-aminoisobutyrate (AIB) and N-methyl-2-aminoisobutyrate (MAIB) were promising lead compounds whose pharmacokinetic parameters warranted investigation. Methods: Control and Pahenu2−/− mice received intraperitoneal NPAA treatments as test compounds (150, 300 and 500 mg/kg, 1 or 7 days) followed by collection of sera, liver and brain. LC–MS analysis was developed to quantify both AIB and MAIB in all matrices, and pharmacokinetic parameters for distribution, partitioning, accumulation and MAIB demethylation were determined. Results: MAIB was partially converted to AIB in vivo. AIB and MAIB partitioned similarly from sera to the brain and liver, with an approximate 10-fold higher accumulation in the liver compared to the brain. In comparison to MAIB, AIB accumulated to approximately 3 to 7-fold higher concentration in the brain. Analysis of the brain and liver revealed a trend toward decreased Phe with increased MAIB serum concentration. Conclusions: Our data support further pharmacokinetic characterization of MAIB and AIB in preparation for additional preclinical safety, toxicity and tolerability studies of both AIB and MAIB.

Abstract Peptaibols are linear non ribosomal peptides which have been the object of intense research efforts regarding their synthesis and the elucidation of the mechanism allowing their insertion in biological membranes. Forty years after their discovery they are still considered as model compounds and suitable probes for the investigation of new approaches aiming to test the efficacy of new coupling reagents, to physically and spectroscopically investigate the way by which they interact with the lipid bilayer and to develop artificial membrane pores. The stable helical secondary structure adopted by the peptaibols turn to be an adequate platform for gaining insight on the structural modifications induced by the substitution of the amide bond by 1,2,3-triazoles, but also for monitoring the impact of newly designed α,α-dialkyl glycine with fluorinated and silylated side chains as 2-aminoisobutyric acid mimic. Peptaibols secondary structure dictated by Aib high content has inspired the development of foldamers. Challenges and investigations on the above mentioned topics are discussed in this brief review. Graphical abstract Image 1 Highlights • Peptaibols contain α,α-dialkyl glycine and act on membranes. • Peptaibol synthesis promotes the use of new coupling reagents. • Insertion of tailor made amino acids allow to decipher the mechanism of interaction. • Fluorine, triazole, silicon containing amino acids. • Peptaibol inspire the synthesis of new α,α-dialkylglycine applied to foldamers. [ABSTRACT FROM AUTHOR]

Far-infrared spectroscopy is a powerful tool complementing the potential of mid-infrared spectroscopy for the search and identification of organic molecules in space. The far-infrared spectra of a total of 29 amino acids are reported in this study. In addition to the spectra of 20 common proteinogenic amino acids, spectra of a selection of nine non-proteinogenic amino acids are also reported, including the 2-aminoisobutyric acid or α-aminoisobutyric acid which, with glycine, form the most abundant amino acids found in meteorites. The present data base of 29 far-infrared spectra may serve as a reference in the search for amino acids in space environments, given the new opportunities that JWST offers for mid- and far-IR spectroscopy. [ABSTRACT FROM AUTHOR]

Activation of Akt has been suggested to produce neuronal protection in cerebral ischemia. Decreasing blood-brain barrier (BBB) disruption has been associated with a better neuronal outcome in cerebral ischemia. We hypothesized that activation of Akt would decrease BBB disruption and contribute to decreasing the size of infarct in the early stage of cerebral ischemia-reperfusion within the therapeutic window. Transient middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. Rats were treated with SC79 (a selective Akt activator which is cell and BBB permeable) 0.05 mg/kg × 3 i.p. or vehicle i.p. perioperatively. After one hour of MCAO and two hours of reperfusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB, molecular weight 104 Da) and the volume of 3 H-dextran (molecular weight 70,000 Da) distribution were determined to measure the degree of BBB disruption. At the same time point, the size of infarction was determined using tetrazolium staining. In an additional group of rats, a higher dose of SC79 (0.5 mg/kg × 3) was administered to determine the size of infarct. Administration of SC79 increased the K i in the ischemic-reperfused cortex (IR-C, +32%, p <  0.05) as well as in the contralateral cortex (CC, +35%, p <  0.05) when compared with the untreated animals with MCAO/reperfusion. The volume of dextran distribution was not significantly changed by SC79. SC79 treatment significantly produced a decrease in the percentage of cortical infarct out of total cortical area (12.7 ± 1.7% vs 6.9 ± 0.9%, p <  0.001). Increasing the dose of SC79 by ten times did not significantly affect the size of cortical infarct. Contrary to our hypothesis, our data demonstrated that SC79 decreased the size of the infarct in the ischemic-reperfused cortex despite an increase in BBB disruption. Our data suggest the importance of activation of Akt for neuronal survival in the early stage of cerebral ischemia-reperfusion within the therapeutic window and that the mechanism of neuroprotection may not be related to the BBB effects of SC79. [ABSTRACT FROM AUTHOR]

Abstract: Helical α‐aminoisobutyric acid (Aib) foldamers show great potential as devices for the communication of conformational information across phospholipid bilayers, but determining their conformation in bilayers remains a challenge. In the present study, Raman, Raman optical activity (ROA), infrared (IR) and vibrational circular dichroism (VCD) spectroscopies have been used to analyze the conformational preferences of Aib foldamers in solution and when interacting with bilayers. A 310‐helix marker band at 1665–1668 cm−1 in Raman spectra was used to show that net helical content increased strongly with oligomer length. ROA and VCD spectra of chiral Aib foldamers provided the chiroptical signature for both left‐ and right‐handed 310‐helices in organic solvents, with VCD establishing that foldamer screw‐sense was preserved when the foldamers became embedded within bilayers. However, the population distribution between different secondary structures was perturbed by the chiral phospholipid. These studies indicate that ROA and VCD spectroscopies are valuable tools for the study of biomimetic structures, such as artificial signal transduction molecules, in phospholipid bilayers. [ABSTRACT FROM AUTHOR]

Backgroud Osteoporosis is one of the bone-metabolic diseases associated with decreased bone renewal and bone mineral density. β-aminoisobutyric acid (BAIBA), a natural thymine catabolite, can reduce inflammation in skeletal muscle and alleviate hepatic endoplasmic reticulum stress. However, the roles of BAIBA in osteoblast proliferation and differentiation remain largely unknown. Methods The cultured MC3T3-E1 cells received various treatments in this study, including BAIBA alone, H 2 O 2 alone, BAIBA plus N -acetyl- l -cysteine and BAIBA plus apocynin. Cell proliferation was determined by CCK-8 assay and 3 H-Thymidine incorporation. Cell differentiation was evaluated by determining mRNA level of differentiation makers and ALP, and ALP activity. Reactive oxygen species (ROS) were determined by DHE staining while superoxide anion level and NAD(P)H oxidase activity were determined by the lucigenin-derived chemiluminescence method. The content of hydrogen peroxide (H 2 O 2 ) was detected using a commercial kit. The level of NOX1, NOX2 and NOX4 was determined by Western-blot or qRT-PCR. Results We show that treatment of BAIBA stimulated the proliferation of MC3T3-E1 osteoprogenitor cells and enhanced the gene expression of osteoblast differentiation markers. Incubation of MC3T3-E1 cells with BAIBA evoked increases in NAD(P)H oxidase-derived reactive oxygen species (ROS). Scavenging of reactive oxygen species ( N -acetyl- l -cysteine) or inhibition of NAD(P)H oxidase (apocynin) abolished the BAIBA-elicited proliferation and differentiation of MC3T3-E1 cells. Conclusion Our results provide the first evidence that BAIBA stimulates proliferation and differentiation of osteoprogenitor cells via activation of NAD(P)H oxidase/ROS signaling. [ABSTRACT FROM AUTHOR]

A monoprotected aminoethyl amine chiral ligand based on an ethylenediamine backbone was developed to achieve Pd-catalyzed enantioselective C- (sp3)-H arylation of cyclopropanecarboxylic and 2- aminoisobutyric acids without using exogenous directing groups. This new chiral catalyst affords new disconnection for preparing diverse chiral carboxylic acids from simple starting materials that are complementary to the various ring forming approaches. [ABSTRACT FROM AUTHOR]

The peptides orexin-A and −B, the endogenous agonists of the orexin receptors, have similar 19‐amino-acid C-termini which retain full maximum response as truncated peptides with only marginally reduced potency, while further N-terminal truncations successively reduce the activity. The peptides have been suggested to bind in an α‐helical conformation, and truncation beyond a certain critical length is likely to disrupt the overall helical structure. In this study, we set out to stabilize the α‐helical conformation of orexin‐A 15–33 via peptide stapling at four different sites. At a suggested hinge region, we varied the length of the cross-linker as well as replaced the staple with two α-aminoisobutyric acid residues. Modifications close to the peptide C‐terminus, which is crucial for activity, were not allowed. However, central and N‐terminal modifications yielded bioactive peptides, albeit with decreased potencies. This provides evidence that the orexin receptors can accommodate and be activated by α-helical peptides. The decrease in potency is likely linked to a stabilization of suboptimal peptide conformation or blocking of peptide backbone–receptor interactions at the hinge region by the helical stabilization or the modified amino acids. [ABSTRACT FROM AUTHOR]

The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp- d -Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide ( PI ) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure–activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus ( PII ) and both the N- and C-termini ( PIII ) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 ( PIV ), 12 ( PV ), and 8 ( PVI ) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII , as well as PI , could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. [ABSTRACT FROM AUTHOR]

The conformational propensities of the Aib residue on the example of two model peptides Ac-Aib-NHMe ( 1) and Ac-Aib-NMe ( 2), were studied by B3LYP and M06-2X functionals, in the gas phase and in the polar solvents. To verify the reliability of selected functionals, we also performed MP2 calculations for the tested molecules in vacuum. Polarizable continuum models (PCM and SMD) were used to estimate the solvent effect. Ramachandran maps were calculated to find all energy minima. Noncovalent intramolecular interactions due to hydrogen-bonds and dipole attractions between carbonyl groups are responsible for the relative stabilities of the conformers. In order to verify the theoretical results, the available conformations of similar X-ray structures from the Cambridge Crystallographic Data Center (CCDC) were analyzed. The results of the calculations show that both derivatives with the Aib residue in the gas phase prefer structures stabilized by intramolecular N-H⋯O hydrogen bonds, i.e., C and C conformations, while polar solvent promotes helical conformation with φ, ψ values equal to +/−60°, +/−40°. In addition, in the case of molecule 2, the helical conformation is the only one available in the polar environment. This result is fully consistent with the X-ray data. [ABSTRACT FROM AUTHOR]

System A consists of three subtypes, sodium-coupled neutral amino acid transporter 1 (SNAT1), SNAT2, and SNAT4, which are all expressed in the placenta. The aim of this study was to evaluate the contributions of each of the three subtypes to total system A-mediated uptake in placental MVM of human and rat, using betaine and l-arginine as subtype-selective inhibitors of SNAT2 and SNAT4, respectively. Appropriate concentrations of betaine and l-arginine for subtype-selective inhibition in SNAT-overexpressing cells were identified. It was found that 10 mM betaine specifically and almost completely inhibited human and rat SNAT2-mediated [C]α-methylaminoisobutyric acid ([C]MeAIB) uptake, while 5 mM l-arginine specifically and completely inhibited [H]glycine uptake via human SNAT4, as well as [C]MeAIB uptake via rat SNAT4. In both human and rat placental MVM vesicles, sodium-dependent uptake of [C]MeAIB was almost completely inhibited by 20 mM unlabeled MeAIB. l-Arginine (5 mM) partly inhibited the uptake in humans, but hardly affected that in rats. Betaine (10 mM) partly inhibited the uptake in rats, but hardly affected it in humans. These results suggest that SNAT1 is most likely the major contributor to system A-mediated MeAIB uptake by human and rat MVM vesicles and that the remaining uptake is mainly mediated by SNAT4 in humans and SNAT2 in rats. Thus, inhibition studies using betaine and l-arginine are useful to characterize the molecular mechanisms of system A-mediated transport. [ABSTRACT FROM AUTHOR]

Objective: β-Aminoisobutyric acid (BAIBA) has shown to modulate uncoupling protein (UCP)-1 expression, which is mainly expressed in white adipose tissue; however, no studies to date have analyzed its potential effect on the main uncoupling protein of skeletal muscle, UCP-3. The main goal of this study was to assess the potential effect of acute aerobic exercise on serum BAIBA and skeletal muscle UCP-3. The secondary goal was to assess the potential involvement of the transcription factors proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor alpha (PPARα), as well as free fatty acids (FFAs) in UCP-3 expression. A tertiary goal of the study was to evaluate the potential effect of consuming a preexercise meal on the outcome of the first 2 objectives.Methods: In a randomized crossover design, untrained participants performed 2 acute cycling sessions (350 kcal at 70% of their VO2peak) after 2 experimental conditions: (1) consumption of a multi-macronutrient shake and (2) a fasting period of 8 hours. Blood samples were taken at baseline, preexercise, postexercise, 1 hour, and 4 hours postexercise, and muscle biopsies were taken at the last 4 time points. UCP-3 protein concentration and expression, as well as the mRNA expression of PGC-1α and PPARα, were measured in muscle, and BAIBA, glucose, and FFA were measured in serum.Results: Aerobic exercise failed to induce a significant effect on serum BAIBA, PGC-1α, and PPARα regardless on the feeding condition. Despite the lack of effect of exercise on the previous variables, UCP-3 expression and protein concentration significantly increased in the shake condition.Conclusion: The expression of human skeletal muscle UCP-3 as a result of exercise might be controlled by factors other than BAIBA. [ABSTRACT FROM AUTHOR]

A series of 12 thiolated oligopeptides of α-aminoisobutyric acid (Aib) were used to make self-assembled monolayers (SAMs) on carefully annealed gold plates. These peptides, which form 310-helices and have a strong dipole moment along the main peptide axis, were devised to give rise from zero to seven C=O⋅⋅⋅H−N intramolecular hydrogen bonds. The orientation of the natural dipole moment of the peptide was controlled by linking the thiolated moiety to either the nitrogen or carbon terminus. To assess the interactions between the chains forming the monolayer and determine the effect of the peptide orientation, the SAMs were characterized by polarization-modulation infrared-reflection absorption spectroscopy, in comparison with the FTIR behavior of the free peptides in solution. The stability of the peptide SAMs toward electroreduction was studied by cyclic voltammetry in 0.1 m NaOH. We show that electrodesorption is significantly affected by both peptide length and orientation in a way consistent with a strong effect exerted by the dipole moment of the peptide. [ABSTRACT FROM AUTHOR]

Acacia holosericea stems with attached phyllodes have potential as a cut foliage line in vase displays. However, they have a short vase life. Wounding that occurs during harvest induces ethylene production and promotes the senescence of many plant tissues, but effects on A. holosericea foliage longevity are not known. Wound ethylene was measured from mechanically injured A. holosericea phyllodes and stems at various developmental stages. Modulation of ethylene production was investigated using chemical inhibitor and promoter treatments. The ethylene binding inhibitor silver thiosulfate increased wound ethylene evolution, but did not differentially affect vase life. Vase life was prolonged by nano silver particles and silver nitrate treatments due to the antibacterial effects of these two Ag + compounds. Treatments with the ethylene synthesis inhibitors α-aminoisobutyric acid and aminoethoxyvinylglycine and with the ethylene binding inhibitor 1-methylcyclopropene had no significant effect on either wound ethylene production or vase life. Treatments with jasmonic acid and methyl jasmonic acid, which can act either synergistically or antagonistically with ethylene, both reduced vase life. Application of exogenous ethylene gas to detached stems induced ethylene production, accelerated senescence, and reduced vase life. However, treatment with the ethylene releasing compound ethephon generally had no effect on vase life. Considered collectively, the results suggest that short longevity of A. holosericea is largely independent of ethylene synthesis at the cutting wound. [ABSTRACT FROM AUTHOR]

The chiral deuterium- and 13 C-isotope-labeled α-aminoisobutyric acids CD 3 -Aib and 13 CH 3 -Aib were enantioselectively synthesized from L-Ala aldimine using simplified Maruoka chiral phase-transfer catalysts. Homo-chiral ( S )-CD 3 -Aib homopeptides, up to decamers, were prepared. A ( R )-CD 3 -Aib polymer and ( S )- 13 CH 3 -Aib polymer were also prepared. Conformational studies on homopeptides using CD spectra and an X-ray crystallographic analysis revealed that the preferred conformations were 3 10 -helical structures comprising equal amounts of right-handed ( P ) and left-handed ( M ) helical-screw structures. The α-carbon chiral centers induced by the D- or 13 C-isotope substitution of Aib were incapable of controlling the helical-screw directions of their oligopeptides and short polymers. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) pathway is essential in neuronal survival and repair in cerebral ischemia. Decreases in blood-brain barrier (BBB) disruption are associated with a decrease in neuronal damage in cerebral ischemia. This study was performed to investigate how pre-inhibition of the mTOR pathway with rapamycin would affect BBB disruption and the size of the infarcted cortical area in the early stage of focal cerebral ischemia-reperfusion using quantitative analysis of BBB disruption. Rats were treated with 20 mg/kg of rapamycin i.p. once a day for 2 days (Rapamycin Group) or vehicle (Control Group) before transient middle cerebral artery (MCA) occlusion. After one hour of MCA occlusion and two hours of reperfusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB) to measure the degree of BBB disruption and the size of the cortical infarct were determined. Ischemia-reperfusion increased the K i in the Rapamycin treated (+15%) as well as in the untreated control group (+13%). However, rapamycin pretreatment moderately decreased K i in the contralateral (−30%) as well as in the ischemic-reperfused (−29%) cortex when compared with the untreated control group. Rapamycin pretreatment substantially increased the percentage of cortical infarct compared with the control group (+56%). Our data suggest that activation of mTOR pathway is necessary for neuronal survival in the early stage of cerebral ischemia-perfusion and that the reason for the enlarged cortical infarct by rapamycin pretreatment may be related to its non-BBB effects on the mTOR pathway. [ABSTRACT FROM AUTHOR]

Glycine (Gly) is incorporated in roughly half of all known peptaibiotic (nonribosomally biosynthesized antibiotic peptides of fungal origin) sequences and is the residue with the greatest conformational flexibility. The conformational space of Aib (α-aminoisobutyric acid) is severely restricted by the second methyl group attached to the Cα atom. Most of the crystal structures containing Aib are N-terminal protected. Deprotection of the N- or C-terminus of peptides may alter the hydrogen-bonding scheme and/or the structure and may facilitate crystallization. The structure reported here for glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid tert-butyl ester, C16H30N4O5, describes the first N-terminal-unprotected (Gly-Aib) n peptide. The achiral peptide could form an intramolecular hydrogen bond between the C=O group of Gly1 and the N-H group of Aib4. This hydrogen bond is found in all tetrapeptides and N-terminal-protected tripeptides containing Aib, apart from one exception. In the present work, this hydrogen bond is not observed (N...O = 5.88 Å). Instead, every molecule is hydrogen bonded to six other symmetry-related molecules with a total of eight hydrogen bonds per molecule. The backbone conformation starts in the right-handed helical region (and the left-handed helical region for the inverted molecule) and reverses the screw sense in the last two residues. [ABSTRACT FROM AUTHOR]