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.

Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-alpha properties / P. Grieco, C. Rossi, S. Gatti, G. Colombo, A. Carlin, E. Novellino, T. Lama, J.M. Lipton, A. Catania. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 48:5(2005 Mar 10), pp. 1384-1388.

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

C. Rossi;S. Gatti;G. Colombo;A. Carlin;
2005-03-10

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.
Anti-Inflammatory Agents, Non-Steroidal ; Antifungal Agents ; Candida albicans ; Melanocyte-Stimulating Hormones ; Peptide Fragments ; Structure-Activity Relationship ; Tumor Necrosis Factor-alpha ; alpha-MSH
Settore MED/09 - Medicina Interna
JOURNAL OF MEDICINAL CHEMISTRY
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/226861
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