Michèle Baudy-Floc'h

Hydrazinoazadipeptides as aromatic solvent gelators

Abstract In the presence of a small amount of HCl, hydrazinoazadipeptides form thermoreversible physical gels with aromatic solvents. These gels are stable to 70–90°C, and can be stored for months. Electron microscopy reveals that in these solvents, pseudopeptides self-assemble into elongated and very thin fibers, which in turn form a three-dimensional network that traps solvent molecules. Infrared studies showed that aggregation is accompanied by the formation of a hydrogen-bonded network between NH and CO of the hydrazinopeptides.

From a marine neuropeptide to antimicrobial pseudopeptides containing aza-β(3)-amino acids: structure and activity

Incorporation of aza-β(3)-amino acids into an endogenous neuropeptide from mollusks (ALSGDAFLRF-NH(2)) with weak antimicrobial activity allows the design of new AMPs sequences. Depending on the nature of the substitution, this can render the pseudopeptides inactive or lead to a drastic enhancement of the antimicrobial activity without high cytotoxicity. Structural studies of the pseudopeptides carried out by NMR and circular dichroism show the impact of aza-β(3)-amino acids on peptide structure. The first three-dimensional structures of pseudopeptides containing aza-β(3)-amino acids in aqueous micellar SDS were determined and demonstrate that the hydrazino turn can be formed in aqueous solution. Thus, AMP activity can be modulated through structural modifications induced by the nature and the position of such amino acid analogues in the peptide sequences.

Antimicrobial peptides in oyster hemolymph: the bacterial connection.

We have explored antimicrobial compounds in oyster hemolymph and purified four active peptides with molecular masses of 4464, 3158, 655 and 636 Da. While no exploitable structural elements were obtained for the former three, a partial amino acid sequence (X-P-P-X-X-I-V) was obtained for the latter, named Cg-636. Due to both its low MM and the presence of exotic amino acid residue (X), we suspected a bacterial origin and tracked cultivable hemolymph-resident bacteria of oyster for their antimicrobial abilities. Supernatants of 224 hemolymph resident bacteria coming from 60 oysters were screened against 10 target bacteria including aquaculture pathogens. Around 2% (5 strains) revealed antimicrobial activities. They belong to Pseudoalteromonas and Vibrio genera. Two closely related strains named hCg-6 and hCg-42 have been shown to produce Bacteriocin-Like Inhibitory Substances (BLIS) even in oyster hemolymph. We report herein first BLIS-producing bacteria isolated from bivalve hemolymph. These results strongly suggest that hemolymph resident bacteria may prevent pathogen establishment and pave the way for considering a role of resident bacteria into bivalve defense.

Ovarian jelly-peptides (OJPs), a new family of regulatory peptides identified in the cephalopod Sepia officinalis

In marine invertebrates, numerous water-borne peptides involved in reproductive behavior have been characterized. In this study, we focused on three ovarian water-borne peptides, released by full-grown oocytes (FGO) in the genital coelom and in the lumen of the oviduct in the cuttlefish Sepia officinalis. The first one (DQVKIVL), was characterized by the monitoring of HPLC purified fraction using a myotropic bioassay. Subsequently, a peptidomic approach consisting of a mass spectrometry comparative screening performed between the peptide content of FGO with that of FGO-conditioned medium, led to the identification of two additional water-borne peptides. The second peptide identified (DEVKIVL) was characterized by MS/MS and the primary structure of the third one (DEVKIVLD) was elucidated by a combination of Edman degradation, acid hydrolysis and MS/MS analysis. Sequence homology, tissue mapping and bioactivity demonstrate that these peptides belong to the same family. DQVKIVL-related-peptides strictly localized in the female genital tract modulate the whole female genital tract and the main nidamental gland contractions. Furthermore, these peptides form a jelly, when resuspended in water. This particular property could play an important role in the kinetics of peptide diffusion in the external medium. Thus, these regulatory peptides were named ovarian jelly-peptides (OJPs).

A simple synthesis of New Push-Pull substituted imidazoles by chemoselective nucleophilic attack of α-cyano epoxides

Abstract A chemoselective reaction of amidines or guanidines with α-cyano epoxides leads to new 4-amino-5-carbethoxy or 4-hydroxy-5-cyano or 4-carbethoxy-5-aryl- imidazoles depending on the steric hindrance of the epoxides and on the reaction medium.

A Complex Set of Sex Pheromones Identified in the Cuttlefish Sepia officinalis

Background The cephalopod mollusk Sepia officinalis can be considered as a relevant model for studying reproduction strategies associated to seasonal migrations. Using transcriptomic and peptidomic approaches, we aim to identify peptide sex pheromones that are thought to induce the aggregation of mature cuttlefish in their egg-laying areas. Results To facilitate the identification of sex pheromones, 576 5′-expressed sequence tags (ESTs) were sequenced from a single cDNA library generated from accessory sex glands of female cuttlefish. Our analysis yielded 223 unique sequences composed of 186 singletons and 37 contigs. Three major redundant ESTs called SPα, SPα′ and SPβ were identified as good candidates for putative sex pheromone transcripts and are part of the 87 unique sequences classified as unknown. The alignment of translated SPα and SPα′ revealed a high level of conservation, with 98.4% identity. Translation led to a 248-amino acid precursor containing six peptides with multiple putative disulfide bonds. The alignment of SPα-α′ with SPβ revealed a partial structural conservation, with 37.3% identity. Translation of SPβ led to a 252-amino acid precursor containing five peptides. The occurrence of a signal peptide on SPα, SPα′ and SPβ showed that the peptides were secreted. RT-PCR and mass spectrometry analyses revealed a co-localization of transcripts and expression products in the oviduct gland. Preliminary in vitro experiments performed on gills and penises revealed target organs involved in mating and ventilation. Conclusions The analysis of the accessory sex gland transcriptome of Sepia officinalis led to the identification of peptidic sex pheromones. Although preliminary functional tests suggested the involvement of the α3 and β2 peptides in ventilation and mating stimulation, further functional investigations will make it possible to identify the complete set of biological activities expected from waterborne pheromones.

Synthese de N-amino maléimides et d'anhydrides maléiques disubstitués à partir d'α-halogéno hydrazides. Etude du mécanisme de la réaction

Abstract α-halohydrazides react with 2-amino pyridine to give symetrically substituted N-amino maleimides. We have shown that this reaction proceeds through the formation of 4-hydroxy imidazopyridines. This result open a new route to dissymetrically substituted N-amino maleimides. The hydrolysis of N-amino maleimides is a good route to substituted maleic anhydrides.

Renal ischemia/reperfusion injury in rats is attenuated by a synthetic glycine derivative.

Renal ischemia/reperfusion is a common cause of acute renal failure. Glycine is an effective anti-inflammatory, cytoprotective agent and is reported to have a beneficial effect against ischemia/reperfusion injury in various organs. Previous research notes that free radicals and inflammatory leukocytes both play important roles in the pathogenesis of renal ischemia/reperfusion injury. To develop new therapeutic agents against renal ischemia/reperfusion injury, we sought to link an antioxidant moiety (nitronyl nitroxide) to glycine in the hope that the resulting glycine-nitronyl nitroxide conjugate (GNN) would provide a synergetic protection against renal ischemia/reperfusion injury. In this manuscript, we report the synthesis and biological evaluation of the GNN conjugate. The biological activity of the GNN conjugate was evaluated in an in vivo rat model of renal ischemia/reperfusion induced injury and oxidative change. Since the GNN conjugate markedly reduced elevated levels of tissue lipid peroxidation and attenuated renal dysfunction in rats subjected to renal ischemia/reperfusion, it might be possible to develop the GNN conjugate into a potential therapeutic agent against renal ischemia/reperfusion injury.

N-Amino indolinones à partir d'arylhydrazides α-halogènes

Abstract N-amino indolinones are obtained in good yield through the reaction of α-halohydrazides with NEt 3 .

First sharpless epoxidation of electrophilic 2-cyanoallylic alcohols

Abstract For the first time we describe the synthesis of asymmetric cyano epoxy alcohols in good yield and high enantiometic excess via a Sharpless epoxidation of electrophilic 2-cyanoallylic alcohols.