Previous research has shown that the immunomodulatory peptide alpha-MSH (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 mol. appeared a promising candidate for therapy of fungal infections and was the subject of a structural study. 1H-NMR and restrained mechanic and dynamic calcns. suggest that the peptide adopts an extended backbone structure with a beta-turn-like structure. These results open a pathway to development of addnl. novel compds. that have candidacidal effects potentially useful against clin. infections.
Three-Dimensional Structure of the a-MSH-derived Candidacidal Peptide [Ac-CKPV]2 / Anna, Catania; Grieco, Paolo; Randazzo, Antonio; Novellino, Ettore; Stefano, Gatti; Claudia, Rossi; Gualtiero, Colombo; JAMES M., Lipton. - In: JOURNAL OF PEPTIDE RESEARCH. - ISSN 1397-002X. - STAMPA. - 66:1(2005), pp. 19-26. [10.1111/j.1399-3011.2005.00265.x]
Three-Dimensional Structure of the a-MSH-derived Candidacidal Peptide [Ac-CKPV]2
GRIECO, PAOLO;RANDAZZO, ANTONIO;NOVELLINO, ETTORE;
2005
Abstract
Previous research has shown that the immunomodulatory peptide alpha-MSH (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 mol. appeared a promising candidate for therapy of fungal infections and was the subject of a structural study. 1H-NMR and restrained mechanic and dynamic calcns. suggest that the peptide adopts an extended backbone structure with a beta-turn-like structure. These results open a pathway to development of addnl. novel compds. that have candidacidal effects potentially useful against clin. infections.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
