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Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-alpha properties.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2005 Mar 10; Vol. 48 (5), pp. 1384-8. - Publication Year :
- 2005
-
Abstract
- Alpha-melanocyte stimulating hormone (alpha-MSH) is an endogenous antiinflammatory peptide with antimicrobial properties. We recently found that a synthetic analogue, [dNal(2')-7, Phe-12]-alpha-MSH (6-13), was considerably more potent in killing Candida albicans, but the anti-cytokine potential of the molecule was not investigated. Because molecules that combine candidacidal and antiinflammatory properties could be very useful in clinical practice, we measured the anti-TNF-alpha potential of [dNal(2')-7, Phe-12]-alpha-MSH (6-13) and explored effects of amino acid deletions and substitutions on both anti-Candida and anti-TNF-alpha activities. The results show that anti-TNF-alpha properties of this candidacidal peptide are only marginally increased relative to the native sequence. Conversely, we found that a closely related candidacidal analogue, [dNal(2')-7, Pro-12]-alpha-MSH (6-13), had enhanced anti-TNF-alpha effects in vitro and in vivo. This peptide, and other melanocortins with a similar dual effect, could be very useful to eradicate infections and, concurrently, reduce inflammatory reactions.
- Subjects :
- Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Antifungal Agents chemistry
Antifungal Agents pharmacology
Candida albicans isolation & purification
Melanocyte-Stimulating Hormones chemistry
Melanocyte-Stimulating Hormones pharmacology
Peptide Fragments chemistry
Peptide Fragments pharmacology
Structure-Activity Relationship
Tumor Necrosis Factor-alpha biosynthesis
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Antifungal Agents chemical synthesis
Candida albicans drug effects
Melanocyte-Stimulating Hormones chemical synthesis
Peptide Fragments chemical synthesis
Tumor Necrosis Factor-alpha antagonists & inhibitors
alpha-MSH chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 48
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15743181
- Full Text :
- https://doi.org/10.1021/jm040890j