title: Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.
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.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Luigia
authors.initials: L
authors.lastname: Auriemma
authors.forename: Antonio
authors.initials: A
authors.lastname: Limatola
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Maro
authors.forename: Francesco
authors.initials: F
authors.lastname: Merlino
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Luca
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Grazia
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Anna
authors.initials: A
authors.lastname: Catania
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D060327:Solid-Phase Synthesis Techniques; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D009842:Oligopeptides; D000521:alpha-MSH