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Antimicrobial actions of α‐MSH peptides – implications for mucocutaneous host defense
Author(s) -
Catania A.,
Grieco P.,
Rossi C.,
Colombo G.,
Gatti S.,
Lipton J. M.
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00212t.x
Subject(s) - antimicrobial peptides , antimicrobial , peptide , melanocortin , innate immune system , beta defensin , adenylyl cyclase , receptor , biology , chemotaxis , peptide sequence , chemistry , biochemistry , microbiology and biotechnology , gene
Endogenous antimicrobial peptides are components of the innate host defense system that prevents microbial penetration before the time‐consuming adaptive immunity starts. We have recently demonstrated that α‐melanocyte‐stimulating hormone (α‐MSH) has antimicrobial effects. The antimicrobial influences of α‐MSH are exerted through a unique mechanism, which appears to be linked to the cAMP‐inducing activity of the peptide. This mechanism mimics the influence of α‐MSH in mammalian cells in which the peptide binds to G‐protein‐linked melanocortin receptors, activates adenylyl cyclase, and increases cAMP. In an attempt to improve the antimicrobial activity of α‐MSH and to better understand the peptide structure–activity relations, we designed and synthesized novel peptide analogs. In this structure–activity study, we discovered several compounds that have greater antimicrobial activity than α‐MSH. The peptide [ D Nal‐7, Phe‐12]‐α‐MSH (6–13) was the most potent of the analogs tested. This compound killed almost 100% of Candida cells and had substantial antimicrobial effects against Gram‐positive and Gram‐negative bacteria. Enhanced antimicrobial activity of the Phe‐12‐substituted peptides was the most distinctive feature relative to effects in mammalian cells. The results are very encouraging in that they show the great potential of α‐MSH peptides as a truly novel class of antimicrobial compounds.