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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Compounds that activate the mouse melanocortin-1 receptor identified by screening a small molecule library based upon the beta-turn.

A library of 951 compounds based upon the beta-turn motif were examined for their ability to stimulate the melanocortin-1 receptor. From this screening process, we have identified two compounds possessing low micromolar agonist activity at the mMC1R. The compound EL1 with racemic Nal(2') in the i + 1 position, DPro in the i + 2 position, and Trp in the i + 3 position possesses an EC(50) of 42.5 +/- 6.9 microM. Compound EL2 with Trp in the i + 1 position, DLys in the i + 2 position, and Phe in the i + 3 position possesses an EC(50) value of 63.4 +/- 26.9 microM. The results of the library screening process are consistent with a hypothesis dating back to the 1980s proposing that a beta-turn conformation involving the melanocortin "Phe-Arg-Trp" core amino acids provides the key recognition element. Additionally, these compounds represent the first nonpeptidic heterocyclic molecules reported to date that are able to activate the MC1R, a melanocyte receptor involved in skin pigmentation and animal coat coloration.[1]

References

  1. Compounds that activate the mouse melanocortin-1 receptor identified by screening a small molecule library based upon the beta-turn. Haskell-Luevano, C., Rosenquist, A., Souers, A., Khong, K.C., Ellman, J.A., Cone, R.D. J. Med. Chem. (1999) [Pubmed]
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