Sophie Faure

The click triazolium peptoid side chain: a strong cis-amide inducer enabling chemical diversity.

Access to homogeneous and discrete folded peptoid structures primarily depends on control of the cis/trans isomerism of backbone tertiary amides. This can be achieved by designing specific side chains capable of forming local interactions with the backbone. This is often undertaken at the expense of side-chain diversity, which is a key advantage of peptoids over other families of peptidomimetics. We report for the first time a positively charged triazolium-type side chain that does not compromise diversity and exhibits the best ability reported to date for inducing the cis conformation. The cis-directing effect was studied in N-acetamide dipeptoid model systems and evaluated in terms of K(cis/trans) using NMR spectroscopy in aprotic and protic solvents. Computational geometry optimization and natural bond orbital analysis in combination with NOESY experiments were consistent with a model in which n → π*(Ar) electronic delocalization [from carbonyl (O(i-1)) to the antibonding orbital (π*) of the triazolium motif on residue i] may be operative. In the computational model (gas-phase) and experimentally in CDCl(3), H-bonding between the triazolium C-H proton and the C(i)═O(i) oxygen was also identified and may act cooperatively with the n → π*(Ar) delocalization, resulting in the absence of the trans rotamers in CDCl(3).

12-Helix folding of cyclobutane beta-amino acid oligomers.

The hexamer and octamer of trans-2-aminocyclobutane carboxylic acid were prepared and their conformational preferences studied experimentally and using molecular modeling. All observations suggest a marked preference for the folding of these oligomers into a well-defined 12-helical conformation, in both solution and the solid state.

Convenient Solution-Phase Synthesis and Conformational Studies of Novel Linear and Cyclic α,β-Alternating Peptoids

The synthesis of a novel family of peptidomimetics composed of linear and cyclic alpha,beta-alternating peptoids is described. Oligomers consisting of up to six peptoid residues (n = 1-3) were synthesized on large scale with use of an efficient iterative solution-phase method and longer oligomers (n = 4, 5) were obtained by the coupling of appropriately protected shorter oligomers. Preliminary conformational studies of these hybrid peptoids are reported.

The tert-butyl side chain: a powerful means to lock peptoid amide bonds in the cis conformation.

The very simple sterically hindered tert-butyl side chain exerts complete control over the peptoid amide geometry which only exists in the cis conformation. It is exemplified in NtBu glycine homo-oligomers and in linear oligopeptoids designed with an alternating cis-trans backbone amide pattern.

Passerini Reaction−Amine Deprotection−Acyl Migration Peptide Assembly: Efficient Formal Synthesis of Cyclotheonamide C

A short, convergent, formal total synthesis of cyclotheonamide C is described. The key linear pentapeptide intermediate is assembled at the same time as the elaboration of the alpha-hydroxyhomoarginine (H-hArg) residue via a three-component Passerini reaction-amine deprotection-O,N-acyl migration strategy.

Expedient Preparation of All Isomers of 2-Aminocyclobutanecarboxylic Acid in Enantiomerically Pure Form

A short, convenient, gram scale protocol has been established to allow facile access to all four stereoisomers of 2-aminocyclobutanecarboxylic acid, each in enantiomerically pure form (ee >99%). Starting from the readily available cis racemate, the procedure combines efficient alpha-phenylethylamine derivative resolution and controlled cis-to-trans epimerization procedures, and proceeds with invariably high yields.

Deleterious genetic influence of CX3CR1 genotypes on HIV-1 disease progression.

We previously reported that patients homozygous for a specific mutation (M280) in the chemokine receptor CX3CR1 progressed to AIDS more rapidly than those with other genotypes. This deleterious effect would predict that a cohort of prevalent patients would be depleted in M280 carriers, because these patients would have disappeared before recruitment. This hypothesis is confirmed in this new study based on the French SEROCO cohort showing that patients homozygous for the M280 allele were rare among the seroprevalent group. These results may explain the conflicting results published on the impact of CX3CR1 polymorphism in seroconverters.

Rapid Assembly of the Polyhydroxylated β-Amino Acid Constituents of Microsclerodermins C, D, and E

A very short and efficient synthesis of protected derivatives of APTO and AETD, the complex polyhydroxylated beta-amino acid residues present in microsclerodermins C, D, and E, is described. The targets are obtained in only five steps, in 23% and 16% overall yields, respectively. The key transformation involves the completely diastereoselective two-carbon homologation of appropriately selected intermediate chiral sulfinimines.

Immobilization of proteases on chitosan for the development of films with anti-biofilm properties

Bacterial resistance due to biofilm formation-particularly Staphylococci biofilms-is associated with multiple problems in medical settings where biofilms can colonize medical indwelling devices and cause nosocomial infections. It was against this backdrop that we explored the anti-biofilm activities of a set of proteases against biofilm formation by Staphylococcus aureus, Listeria monocytogenes and Pseudomonas aeruginosa. The selected screened enzymes were immobilized on chitosan to obtain films with anti-biofilm activities. Immobilization efficiency was about 94% for protease from Bacillus licheniformis and reached up to 96% for Neutrase. In vitro assays performed in brain heart infusion (BHI) broth using the Biofilm Ring Test highlighted that immobilized enzymes were efficient against biofilms of Staphylococci cultures, especially protease from B. licheniformis and Neutrase from Bacillus amyloliquefaciens.

Cyclic α,β-peptoid octamers with differing side chain patterns: synthesis and conformational investigation

The solution-phase synthesis and cyclisation of three α,β-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids. The X-ray crystal structure of cyclic octamer C, the first high-resolution structure for the α,β-peptoid backbone, was also obtained from methanol. Combined solid- and solution-phase studies allowed the identification of the N-2-(benzyloxy)ethyl side chain on the β-residue of the heterogeneous backbone as a key structural feature driving the increased conformational stability for octamer C.