Design, Synthesis and Exploration of Amphiphilic α/γ4 Hybrid Helices as a Potent Antibacterial Agent

Abstract

The emergence of drug resistant microorganisms poses a great worldwide threat and created an immediate need for the development of novel antibiotics with different mechanism of action. Microbial resistance to the antibiotics can affect any one regardless of the gender, age and the country. In addition, microbial resistance to the known antibiotics also imperil the progress in medical and health sciences. In this context, the broad spectrum antimicrobial activity shown by the cationic host-defence antimicrobial peptides (AMPs) have attracted considerable attention. Among various types of host-defence peptides, helical motifs have been an active components of a large family of cationic antimicrobial peptides. These peptides have shown excellent antibacterial properties, however they suffer from non-specificity, higher hemolytic activity and poor bioavailability. In this project, we have designed proteolytically stable hybrid peptide 12-helical foldamers and investigated their antimicrobial activities against various bacterial strains and also examine the haemolytic activity and their proteolytic stability against serine protease trypsin. In comparison to α-peptide counterpart, the hybrid peptide foldamers showed potent antibacterial activity and showed increased stability against the protease trypsin.