Structure and antimicrobial properties of multivalent short peptides

Abstract

The emergence of multidrug-resistant (MDR) strains continues to threaten human health. Along with many efforts directed towards the development of antimicrobial peptides (AMPs) as potential antibiotics, we have designed and tested several series of multivalent AMPs in comparison with the natural AMP, indolicidin. Constructs include multivalent displays with different sequences, repeats and scaffolds, including dendrimers, brush-like structures and polymeric displays constructed by linking various peptides to polymaleic anhydride (PMA). A branched tetramer of dipeptides (RW)_4D demonstrates the highest level of effectiveness among the constructs of this study. The results also show that under extended exposure to sublethal doses of (RW)_4D and indolicidin over a 400 generations period, MDR strains elicit much lower levels of resistance than to traditional antibiotics or disinfectants such as ciprofloxacin, vancomycin, chlorhexidine and gentamicin.