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 language | English |
|---|---|
| Pages (from-to) | 1384-1388 |
| Number of pages | 5 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 48 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 10 2005 |
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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 journal › Article
}
TY - JOUR
T1 - Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-α properties
AU - Grieco, Paolo
AU - Rossi, Claudia
AU - Gatti, Stefano
AU - Colombo, Gualtiero
AU - Carlin, Andrea
AU - Novellino, Ettore
AU - Lama, Teresa
AU - Lipton, James M.
AU - Catania, Anna
PY - 2005/3/10
Y1 - 2005/3/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=14944339505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14944339505&partnerID=8YFLogxK
U2 - 10.1021/jm040890j
DO - 10.1021/jm040890j
M3 - Article
C2 - 15743181
AN - SCOPUS:14944339505
VL - 48
SP - 1384
EP - 1388
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 5
ER -