Arginine/Tryptophan‐Rich Cyclic α/β‐Antimicrobial Peptides: The Roles of Hydrogen Bonding and Hydrophobic/Hydrophilic Solvent‐Accessible Surface Areas upon Activity and Membrane Selectivity

摘要: The bacterial selectivity of an amphiphilic library small cyclic α/β-tetra-, α/β-penta-, and α/β-hexapeptides rich in arginine/tryptophan (Arg/Trp) residues, which contains asymmetric backbone configurations differ hydrophobicity alternating d,l-amino acids, was investigated against Bacillus subtilis Escherichia coli. structural analyses showed that the peptides tend to form assemblies different shapes. All-l-peptides, especially most hydrophobic pentamers, were more strongly anti-B. subtilis. With exception cyclo(Phe-d-Trp-β3 hArg-Arg-d-Trp) (Phe=phenylalanine), had no effects on inner membrane E. coli, but lyzed lipopolysaccharide layer according their activity pattern. activities adversely changed with a decrease number amide intramolecular hydrogen bonds diastereomeric ratio hydrophobic/hydrophilic solvent-accessible surface areas. remarkable enhanced entropic contribution for partitioning least conformationally constrained cyclo(Trp-d-Phe-β3 hTrp-Arg-d-Arg) sequence into membranes supported strong self-assembly behavior, therefore making peptide less penetrable through E. coli outer layer.