Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac-CKPV]2.

The journal of peptide research : official journal of the American Peptide Society200517 citationsPMID: 15946192

Plain Language Summary

Researchers determined the three-dimensional structure of [Ac-CKPV]₂, a dimeric candidacidal peptide derived from alpha-MSH's C-terminal KPV sequence. This dimer, created by linking two KPV units with a Cys-Cys linker, showed excellent activity against azole-resistant Candida species. NMR studies and molecular dynamics calculations revealed that the peptide adopts an extended backbone structure with a beta-turn-like conformation. This structural characterization opens pathways for developing novel antifungal compounds based on the KPV scaffold.

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

Catania, A; Grieco, P; Randazzo, A; Novellino, E; Gatti, S; Rossi, C; Colombo, G; Lipton, J M