alpha-Melanocyte-stimulating hormone (alpha-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly demonstrated that alpha-MSH and its C-terminal sequence Lys-Pro-Val [alpha-MSH(11-13)] have antimicrobial effects against two major and representative pathogens: Staphylococcus aureus and Candida albicans. Successively, in an attempt to improve the candidacidal activity of alpha-MSH and to better understand the peptide structure-antifungal activity relations, we have recently designed and synthesized novel peptide analogues. We focused on the sequence alpha-MSH(6-13), which contains the invariant melanocortin core sequence His-Phe-Arg-Trp (6-9) and also contains the sequence Lys-Pro-Val (11-13) important for antimicrobial activity. In that structure-activity study, we discovered several compounds that have greater candidacidal activity than alpha-MSH, among which the peptide [D-Nal-7,Phe-12]-alpha-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, alpha-MSH(6-13) (1), [D-Nal-7,Phe-12]-alpha-MSH(6-13) (2) and [D-Nal-7,Asp-12]-alpha-MSH(6-13) (3). Peptides were chosen on the basis of their candidacidal activities and were studied in membrane mimetic environment (SDS micelles). Different turn structures were observed for the three peptides and a conformation-activity model was developed based on these results. This study offers a structural basis for the design of novel peptide and non-peptide analogues to be used as new antimicrobial agents.

Structure-function Relationships and Conformational Properties of alpha-MSH(6-13) Analogues with Candidacidal Activity / Carotenuto, Alfonso; Saviello, M. R.; Auriemma, L.; Campiglia, P.; Catania, A.; Novellino, Ettore; Grieco, Paolo. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0277. - STAMPA. - 69:1(2007), pp. 68-74. [10.1111/j.1747-0285.2007.00473.x]

Structure-function Relationships and Conformational Properties of alpha-MSH(6-13) Analogues with Candidacidal Activity

CAROTENUTO, ALFONSO
Primo
;
NOVELLINO, ETTORE;GRIECO, PAOLO
2007

Abstract

alpha-Melanocyte-stimulating hormone (alpha-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly demonstrated that alpha-MSH and its C-terminal sequence Lys-Pro-Val [alpha-MSH(11-13)] have antimicrobial effects against two major and representative pathogens: Staphylococcus aureus and Candida albicans. Successively, in an attempt to improve the candidacidal activity of alpha-MSH and to better understand the peptide structure-antifungal activity relations, we have recently designed and synthesized novel peptide analogues. We focused on the sequence alpha-MSH(6-13), which contains the invariant melanocortin core sequence His-Phe-Arg-Trp (6-9) and also contains the sequence Lys-Pro-Val (11-13) important for antimicrobial activity. In that structure-activity study, we discovered several compounds that have greater candidacidal activity than alpha-MSH, among which the peptide [D-Nal-7,Phe-12]-alpha-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, alpha-MSH(6-13) (1), [D-Nal-7,Phe-12]-alpha-MSH(6-13) (2) and [D-Nal-7,Asp-12]-alpha-MSH(6-13) (3). Peptides were chosen on the basis of their candidacidal activities and were studied in membrane mimetic environment (SDS micelles). Different turn structures were observed for the three peptides and a conformation-activity model was developed based on these results. This study offers a structural basis for the design of novel peptide and non-peptide analogues to be used as new antimicrobial agents.
2007
Structure-function Relationships and Conformational Properties of alpha-MSH(6-13) Analogues with Candidacidal Activity / Carotenuto, Alfonso; Saviello, M. R.; Auriemma, L.; Campiglia, P.; Catania, A.; Novellino, Ettore; Grieco, Paolo. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0277. - STAMPA. - 69:1(2007), pp. 68-74. [10.1111/j.1747-0285.2007.00473.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/201290
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