Novel α-melanocyte stimulating hormone peptide analogues with high candidacidal activity

Paolo Grieco, Claudia Rossi, Gualtiero Colombo, Stefano Gatti, Ettore Novellino, James M. Lipton, Anna Catania

Research output: Contribution to journalArticlepeer-review

Abstract

α-Melanocyte stimulating hormone (α-MSH) is an endogenous linear tridecapeptide with potent antiinflammatory effects. We recently demonstrated that α-MSH and its C-terminal sequence Lys-Pro-Val (α-MSH (11-13)) have antimicrobial effects against two major and representative pathogens: Staphylococcus aureus and Candida albicans. In an attempt to improve the candidacidal activity of α-MSH and to better understand the peptide structure-antifungal activity relations, we designed and synthesized novel peptide analogues. Because previous data suggested that antimicrobial effects of α-MSH were receptor-mediated, we chose to focus on the sequence α-MSH (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors and also contains the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity. In this structure-activity study, we discovered several compounds that have greater candidacidal activity than α-MSH. The peptide [D-Nal-7,Phe-12]-α-MSH (6-13) was the most potent of the analogues tested. The present results are very encouraging because they show the great potential of these peptides as a truly novel class of candidacidal compounds.

Original languageEnglish
Pages (from-to)850-855
Number of pages6
JournalJournal of Medicinal Chemistry
Volume46
Issue number5
DOIs
Publication statusPublished - Feb 27 2003

ASJC Scopus subject areas

  • Organic Chemistry

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