Enhanced antimicrobial activity of a peptide derived from human lysozyme by arylation of its tryptophan residues. (19th January 2016)

• Record Type: Journal Article
• Authors: González, Rodrigo; Mendive‐Tapia, Lorena; Pastrian, María B; Albericio, Fernando; Lavilla, Rodolfo; Cascone, Osvaldo; Iannucci, Nancy B
• Is Part Of: Journal of peptide science. Volume 22:Number 2(2016:Feb.)
• Page Start: 123
• Page End: 128
• Publication Date: 2016-01-19
• Subjects: peptide -- human lysozyme -- arylation -- tryptophan -- antimicrobial activity; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2850
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Antimicrobial peptides are valuable agents to fight antibiotic resistance. These amphipatic species display positively charged and hydrophobic amino acids. Here, we enhance the local hydrophobicity of a model peptide derived from human lysozyme (107RKWVWWRNR115) by arylation of its tryptophan (Trp) residues, which renders a positive effect on Staphylococcus aureus and Staphylococcus epidermidis growth inhibition. This site‐selective modification was accessed by solid‐phase peptide synthesis using the non‐proteinogenic amino acid 2‐aryltryptophan, generated by direct C‐H activation from protected Trp. The modification brought about a relevant increase in growth inhibition: S. aureus was fully inhibited by arylation of Trp 112 and by only 10% by arylation of Trp 109 or 111, respect to the non‐arylated peptide. On the other hand, S. epidermidis was fully inhibited by the three arylated peptides and the parent peptide. The minimum inhibitory concentration was significantly reduced for S. aureus depending on the arylation site. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Abstract : Selective arylation of a Trp residue in an antimicrobial peptide results in a relevant increase of its biological activity.