TY - JOUR
T1 - Structure-function relationships and conformational properties of α-MSH(6-13) analogues with candidacidal activity
AU - Carotenuto, Alfonso
AU - Saviello, Maria Rosaria
AU - Auriemma, Luigia
AU - Campiglia, Pietro
AU - Catania, Anna
AU - Novellino, Ettore
AU - Grieco, Paolo
PY - 2007/1
Y1 - 2007/1
N2 - α-Melanocyte-stimulating hormone (α-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly demonstrated that α-MSH and its C-terminal sequence Lys-Pro-Val [α-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 α-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 α-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 α-MSH, among which the peptide [d-Nal-7,Phe-12]-α-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, α-MSH(6-13) (1), [d-Nal-7,Phe-12]-α-MSH(6-13) (2) and [d-Nal-7,Asp-12]-α-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.
AB - α-Melanocyte-stimulating hormone (α-MSH) is an endogenous linear tridecapeptide with potent anti-inflammatory effects. We firstly demonstrated that α-MSH and its C-terminal sequence Lys-Pro-Val [α-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 α-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 α-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 α-MSH, among which the peptide [d-Nal-7,Phe-12]-α-MSH(6-13) was the most potent. Here, we report a detailed conformational analysis by spectroscopic and computational methods of three peptides, α-MSH(6-13) (1), [d-Nal-7,Phe-12]-α-MSH(6-13) (2) and [d-Nal-7,Asp-12]-α-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.
KW - Alpha-MSH analogues
KW - Candidacidal activity
KW - Conformational studies
KW - SDS micellas
UR - http://www.scopus.com/inward/record.url?scp=33847092018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847092018&partnerID=8YFLogxK
U2 - 10.1111/j.1747-0285.2007.00473.x
DO - 10.1111/j.1747-0285.2007.00473.x
M3 - Article
C2 - 17313459
AN - SCOPUS:33847092018
VL - 69
SP - 68
EP - 74
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 1
ER -