The melanocortin pathway has emerged during this past decade as an important target area for the discovery and development of therapeutic agents related to obesity and type 2 diabetes. This peptide-G-protein coupled receptor (GPCR) pathway has evolved from peptide-based ligands to small molecules possessing a variety of different molecular scaffolds. Herein, we summarize the originating hypothesis of the importance of the reverse β-turn secondary structure for agonist ligand potency at the melanocortin receptors and how that information was utilized for the discovery of small molecules based upon this type of turn structure.
Bibliographical noteFunding Information:
We acknowledge financial support from NIH Grants RO1DK57080, RO1DK64250, RO1DK063974, and an American Diabetes Research Award. We thank Mic E. Mouse for his inspirational thoughts.
Copyright 2009 Elsevier B.V., All rights reserved.
- Melanocortin receptors