Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-α properties

Paolo Grieco, Claudia Rossi, Stefano Gatti, Gualtiero Colombo, Andrea Carlin, Ettore Novellino, Teresa Lama, James M. Lipton, Anna Catania

Research output: Contribution to journalArticle

Abstract

α-Melanocyte stimulating hormone (α-MSH) is an endogenous antiinflammatory peptide with antimicrobial properties. We recently found that a synthetic analogue, [DNal(2′)-7, Phe-12]-α-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-α potential of [DNal(2′)-7, Phe-12]-α-MSH (6-13) and explored effects of amino acid deletions and substitutions on both anti-Candida and anti-TNF-α activities. The results show that anti-TNF-α 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]-α-MSH (6-13), had enhanced anti-TNF-α 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.

Original languageEnglish
Pages (from-to)1384-1388
Number of pages5
JournalJournal of Medicinal Chemistry
Volume48
Issue number5
DOIs
Publication statusPublished - Mar 10 2005

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Melanocortins
Melanocyte-Stimulating Hormones
Peptides
Candida
Anti-Inflammatory Agents
Molecules
Amino Acid Substitution
Candida albicans
Substitution reactions
Cytokines
Amino Acids
Infection

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-α properties. / Grieco, Paolo; Rossi, Claudia; Gatti, Stefano; Colombo, Gualtiero; Carlin, Andrea; Novellino, Ettore; Lama, Teresa; Lipton, James M.; Catania, Anna.

In: Journal of Medicinal Chemistry, Vol. 48, No. 5, 10.03.2005, p. 1384-1388.

Research output: Contribution to journalArticle

Grieco, P, Rossi, C, Gatti, S, Colombo, G, Carlin, A, Novellino, E, Lama, T, Lipton, JM & Catania, A 2005, 'Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-α properties', Journal of Medicinal Chemistry, vol. 48, no. 5, pp. 1384-1388. https://doi.org/10.1021/jm040890j
Grieco, Paolo ; Rossi, Claudia ; Gatti, Stefano ; Colombo, Gualtiero ; Carlin, Andrea ; Novellino, Ettore ; Lama, Teresa ; Lipton, James M. ; Catania, Anna. / Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-α properties. In: Journal of Medicinal Chemistry. 2005 ; Vol. 48, No. 5. pp. 1384-1388.
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