Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 68-74 |
| Number of pages | 7 |
| Journal | Chemical Biology and Drug Design |
| Volume | 69 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2007 |
Fingerprint
Keywords
- Alpha-MSH analogues
- Candidacidal activity
- Conformational studies
- SDS micellas
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
Cite this
Structure-function relationships and conformational properties of α-MSH(6-13) analogues with candidacidal activity. / Carotenuto, Alfonso; Saviello, Maria Rosaria; Auriemma, Luigia; Campiglia, Pietro; Catania, Anna; Novellino, Ettore; Grieco, Paolo.
In: Chemical Biology and Drug Design, Vol. 69, No. 1, 01.2007, p. 68-74.Research output: Contribution to journal › Article
}
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 -