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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere61614
JournalPLoS One
Issue number4
Publication statusPublished - Apr 23 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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