Novel α-MSH peptide analogues with broad spectrum antimicrobial activity

Paolo Grieco; Alfonso Carotenuto; Luigia Auriemma; Antonio Limatola; Salvatore Di Maro; Francesco Merlino; Maria Luisa Mangoni; Vincenzo Luca; Antonio Di Grazia; Stefano Gatti; Pietro Campiglia; Isabel Gomez-Monterrey; Ettore Novellino; Anna Catania

doi:10.1371/journal.pone.0061614

Novel α-MSH peptide analogues with broad spectrum antimicrobial activity

PLoS One. 2013 Apr 23;8(4):e61614. doi: 10.1371/journal.pone.0061614. Print 2013.

Authors

Paolo Grieco¹, Alfonso Carotenuto, Luigia Auriemma, Antonio Limatola, Salvatore Di Maro, Francesco Merlino, Maria Luisa Mangoni, Vincenzo Luca, Antonio Di Grazia, Stefano Gatti, Pietro Campiglia, Isabel Gomez-Monterrey, Ettore Novellino, Anna Catania

Affiliation

¹ Department of Pharmacy, University of Naples Federico II, Naples, Italy.

Abstract

Previous investigations indicate that α-melanocyte-stimulating hormone (α-MSH) and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2')-7, Phe-12]-MSH(6-13) sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of α-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology
Candida / drug effects
Candida / growth & development
Candida albicans / drug effects
Candida albicans / growth & development
Candida glabrata / drug effects
Candida glabrata / growth & development
Cell Line
Cell Survival / drug effects
Erythrocytes / cytology
Erythrocytes / drug effects
Gram-Negative Bacteria / drug effects
Gram-Negative Bacteria / growth & development
Gram-Positive Bacteria / drug effects
Gram-Positive Bacteria / growth & development
Hemolysis / drug effects
Humans
Keratinocytes / cytology
Keratinocytes / drug effects
Microbial Sensitivity Tests
Models, Molecular
Molecular Mimicry
Oligopeptides / chemical synthesis
Oligopeptides / chemistry*
Oligopeptides / pharmacology
Solid-Phase Synthesis Techniques
Structure-Activity Relationship
alpha-MSH / chemistry*

Substances

Anti-Infective Agents
Oligopeptides
alpha-MSH

Grants and funding

This work was supported by Italian Ministry of Education, University and Research (PRIN 2008, 2010MCLBCZ_002) and by Fondazione Fiera Milano, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.