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. 2009 Sep 1;19(17):5176-81.
doi: 10.1016/j.bmcl.2009.07.025. Epub 2009 Jul 9.

Semi-rigid tripeptide agonists of melanocortin receptors

Andrew R Ruwe  1 , Leonid Koikov, Zalfa Abdel-Malek, Carrie Haskell-Luevano, Marvin L Dirain, Federico Portillo, Zhimin Xiang, Matt Wortman, James J Knittel
Affiliations

Semi-rigid tripeptide agonists of melanocortin receptors

Andrew R Ruwe et al. Bioorg Med Chem Lett. .

Abstract

A series of 30 RCO-HfR-NH(2) derivatives show preference for the mouse MC1R vs MC3-5Rs. trans-4-HOC(6)H(4)CH=CHCO-HfR-NH(2) (13) [EC(50) (nM): MC1R 83, MC3R 20500, MC4R 18130 and MC5R 935; ratio 1:246:217:11] is 11 times more potent than the lead compound LK-394 Ph(CH(2))(3)CO-HfR-NH(2) (2) and only 11 times less potent than the native tridecapeptide alpha-MSH at mMC1R. Differences in conformations of 2 and 13 are discussed.

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Figures

Figure 1
Figure 1
Conformations within 5 kcal/mol: a. Ph(CH2)3CO-His-D-Phe-Arg-NH2 (2), b. trans-4-HOC6H4CH=CHCO-His-D-Phe-Arg-NH2 (13).
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