ISSN:
1600-0625
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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 [DNal-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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0906-6705.2004.00212t.x
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