Design, synthesis, and biological evaluation of stable β^6.3-Helices: Discovery of non-hemolytic antibacterial peptides.

ABSTRACT: Gramicidin A, a topical antibiotic made from alternating L and D amino acids, is characterized by its wide central pore; upon insertion into membranes, it forms channels that disrupts ion gradients. We present helical peptidomimetics with this characteristic wide central pore that have been designed to mimic gramicidin A channels. Mimetics were designed using molecular modeling focused on oligomers of heterochiral dipeptides of proline analogs, in particular azaproline (AzPro). Molecular Dynamics simulations in water confirmed the stability of the designed helices. A sixteen-residue Formyl-(AzPro-Pro)₈-NHCH₂CH₂OH helix was synthesized as well as a full thirty-two residue Cbz-(AzPro-Pro)₁₆-O^tBu channels. No liposomal lysis activity was

SUBMITTER: Reddy DN 

PROVIDER: S-EPMC8366898 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature