Structure-function relationships and conformational properties of α-MSH(6-13) analogues with candidacidal activity

Alfonso Carotenuto, Maria Rosaria Saviello, Luigia Auriemma, Pietro Campiglia, Anna Catania, Ettore Novellino, Paolo Grieco

Research output: Contribution to journalArticle

Abstract

α-Melanocyte-stimulating hormone (α-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly 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. Successively, in an attempt to improve the candidacidal activity of α-MSH and to better understand the peptide structure-antifungal activity relations, we have recently designed and synthesized novel peptide analogues. We focused on the sequence α-MSH(6-13), which contains the invariant melanocortin core sequence His-Phe-Arg-Trp (6-9) and also contains the sequence Lys-Pro-Val (11-13) important for antimicrobial activity. In that structure-activity study, we discovered several compounds that have greater candidacidal activity than α-MSH, among which the peptide [d-Nal-7,Phe-12]-α-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, α-MSH(6-13) (1), [d-Nal-7,Phe-12]-α-MSH(6-13) (2) and [d-Nal-7,Asp-12]-α-MSH(6-13) (3). Peptides were chosen on the basis of their candidacidal activities and were studied in membrane mimetic environment (SDS micelles). Different turn structures were observed for the three peptides and a conformation-activity model was developed based on these results. This study offers a structural basis for the design of novel peptide and non-peptide analogues to be used as new antimicrobial agents.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalChemical Biology and Drug Design
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Alpha-MSH analogues
  • Candidacidal activity
  • Conformational studies
  • SDS micellas

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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