Simona Oancea

Synthesis and conformational study of homo-peptides based on (S)-Bin, a C2-symmetric binaphthyl-derived Cα,α-disubstituted glycine with only axial chirality

Abstract We synthesised the [( S )-Bin] n ( n =2–5) homo-peptides by solution methods. Only the acid fluoride derivative Fmoc-( S )-Bin-F could be efficiently coupled with H-[( S )-Bin] n -OMe ( n =2–4). Spectroscopic experimental analyses of the [( S )-Bin] n homo-peptides in solution performed by CD, FT-IR absorption, and VCD, supported by VCD calculations, confirmed the ( S ) configuration of the Bin residues and identified the most largely populated secondary structures as right-handed β-turns which eventually evolve to 3 10 -helices in the highest oligomers.

Main‐Chain Length Control of Conformation, Membrane Activity, and Antibiotic Properties of Lipo­peptaibol Sequential Analogues

To investigate the effect of backbone length and amphiphilicity on the 3D structure, membrane permeability, and antibacterial properties of trichogins, a subclass of lipopeptaibols, we prepared, by the segment condensation approach in solution and chemically characterized, a set of Nα‐1‐octanoylated ‐X‐(GLUG)n‐I‐L‐ ( X=G or U where U=Aib; n=1–4) sequential peptide esters. In parallel, the 12‐mer (UGGL)3 aneurism peptide, an analogue of the 11‐mer sequential peptide (n=2) with an amino acid insertion was also synthesized and studied. By FT‐IR absorption technique, we clearly showed that, in CDCl3 solution, all peptides essentially populate intramolecularly H‐bonded, helical conformations. Moreover, CD spectroscopy indicates that all peptides, with the single exception of the shortest oligomer (the heptamer), adopt mixed 310‐/α‐helical structures, to an extent approximately correlating with main‐chain length, in MeOH solution and sodium dodecylsulfate (SDS) micelles. Significant membrane permeability properties were found only for the three longest GLUG‐based peptides, with the 15‐mer oligomer (n=4) resulting the most active. The lack of activity exhibited by the aneurism peptide in this experiment strongly suggests a relevant role for the sequence amphiphilicity. In addition, antibacterial activity and selectivity were highlighted and demonstrated to be dependent on peptide main‐chain length and amphiphilicity, in the sense that the two shortest GLUG‐based homologues are active against Gram‐positive strains, whereas the two longest homologues are able to penetrate the membranes of the Gram‐negative strains, and the UGGL‐based aneurism peptide is inactive.