Structure-activity relationship analysis of a novel antimicrobial peptide derived from the 107-115 h-Lysozyme fragment.

IANNUCCI, N.B.; CURTO L.M.; ALBERICIO, F; CASCONE, O; DELFINO J.M.

Hawaii

Conferencia; 23rd American Peptide Symposium; 2013

Novel antimicrobial peptides are valuable molecules for developing anti-infective drugs to counteract the contemporary spread of microbial drug-resistance. We have previously reported a novel peptide derived from the 107-115 human lysozyme (hLz) fragment which displays 20-fold increased anti-staphylococcal activity1. The conformational analysis of this peptide - assayed by circular dicroism in the presence of an α-helical secondary structure inducing cosolvent (TFE), and lipid:detergent micelles composed by DMPC and DMPC/DMPA - shows a noteworthy correlation between induced helical conformation and anti-staphylococcal activity. This result highlights the role of the peptide?s secondary structure in the interaction with the bacterial plasma membrane to trigger its lethal effect. This knowledge might contribute to the rational design of a new generation of antimicrobial peptides with increased effectiveness developed by simple screening tools from natural sources. The sequences of peptides 107-115 hLz and [K108W111] 107-115 hLz: 107 115 107-115 hLz RAWVAWRNR-NH2 [K108W111] 107-115 hLz RKWVWWRNR-NH2 1. González R, Albericio F, Cascone O, Iannucci N. Improved Antimicrobial Activity of h-Lysozyme (107-115) by Rational Ala Substitution J. Pept. Sci. 2010, 16, 424?429.