Structure-function relationships and engineering of host-defense peptides

Abstract

Over the years, fatalities due to microbial infections have been reduced considerably due to the availability of a large number of potent antibiotics. The mechanism of action of these antibiotics involves either inhibition of bacterial cell wall synthesis, protein and nucleic acid biosynthesis or enzyme activities crucial to bacterial metabolism. Unfortunately, in recent years, microorganisms have developed resistance to a large number of therapeutically used antibiotics which were earlier very effective. Hence, the search for new molecules against which resistance may not develop easily is imperative. Species across the evolutionary scale from insects to mammals use peptides to combat bacteria. The endogenous antibacterial peptides exert their activity by permeabilizing the bacterial membranes. In this review, the approaches that have been employed in engineering endogenous antibacterial peptides to get molecules with improved activity, the biophysical properties that are responsible for activity and the possible therapeutic use of these class of peptides are discussed.