Our research has focused upon the in vitro pharmacological characterization of 70 human melanocortin-4 receptor (hMC4R) single nucleotide polymorphisms (SNPs) to determine the potential molecular mechanism(s) that might associate a particular SNP with obesity. These include decreased cell surface expression and changes in endogenous agonist/antagonist ligand molecular recognition and potency/efficacy. Experimental approaches include the discovery of agonists (peptide and small molecule) that can functionally rescue hMC4R SNPs that do not respond normally to endogenous agonists using both a targeted design approach and a combinatorial screening approach. Our progress towards these efforts and the lessons we have learned will be presented.

Characterization of 70 human melanocortin-4 receptor polymorphisms and the lessons learned

245th National Meeting (2013)

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