title: Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac-CKPV]2.
abstract: Previous research has shown that the immunomodulatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its carboxy-terminal tripeptide KPV (Lys-Pro-Val alpha-MSH11-13) have antimicrobial influences. By inserting a Cys-Cys linker between two units of KPV, we designed the dimer [Ac-CKPV]2 that showed excellent candidacidal effects in pilot tests and was the subject of further investigations. [Ac-CKPV]2 was active against azole-resistant Candida spp. Therefore, the molecule appeared a promising candidate for therapy of fungal infections and was the subject of a structural study. 1H-NMR and restrained mechanic and dynamic calculations suggest that the peptide adopts an extended backbone structure with a beta-turn-like structure. These results open a pathway to development of additional novel compounds that have candidacidal effects potentially useful against clinical infections.
authors.affiliation: Division of Internal Medicine, Ospedale Maggiore di Milano IRCCS, 20122 Milano, Italy. anna.catania@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Catania
authors.forename: P
authors.initials: P
authors.lastname: Grieco
authors.forename: A
authors.initials: A
authors.lastname: Randazzo
authors.forename: E
authors.initials: E
authors.lastname: Novellino
authors.forename: S
authors.initials: S
authors.lastname: Gatti
authors.forename: C
authors.initials: C
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Colombo
authors.forename: J M
authors.initials: JM
authors.lastname: Lipton
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C504266:(Ac-CKPV)2; D000935:Antifungal Agents; D009842:Oligopeptides; D000521:alpha-MSH