Design and development of new polymeric materials with potential antimicrobial and/or antifungal activity

Abstract

This PhD project is focused on the development of new polymeric materials with antibacterial and antifungal activity. The first part of the work was dedicated to the synthesis and the insertion of a modified amino acid into an antimicrobial peptide (AMP), with the aim to retain the action mechanism on bacterial membranes. Understanding the mechanism of action of AMPs is important for the rational design of new drugs. For this reason, I have collected structural properties, antimicrobial activity values and biological origin of antimicrobial peptides from published data. I have calculated the most relevant chemical physical properties like charge, hydrophobic moment, helicity, flexibility, isoelectric point, Boman and instability index and penetration capabilities. This data collection work permitted us to create YADAMP (www.yadamp.unisa.it), a web database with detailed informations on AMPs. YADAMP database contains the highest number of active sequences with proven antimicrobial activity. YADAMP peremitted me to do a work of data mining that end up with the choice of a peptide, a defensine, to be used as template for developing a new photoresponsive peptide. The peptide, hereafter indicated as ALY, is a short α-helix, membrane active AMP with a tyrosine in the sequence. I have developed the modified analogue replacing the tyrosine by a modified tyrosine with azobenzene group in the side chain. The modified amino acid, named Fmoc-azoTyr, was synthesized according to the classic scheme of diazocopulation reactions. I have chosen the azobenzene group because it permits a reversible trans to cis photochemical isomerization... [edited by author]