Peptoid NPhe⁴ in AGRP-Based c[Pro¹-Arg²-Phe³-Phe⁴-Xxx⁵-Ala⁶-Phe⁷-DPro⁸] Scaffolds Maintain Mouse MC4R Antagonist Potency.

ABSTRACT: The melanocortin receptors are involved in numerous physiological functions and are regulated by agonists derived from the proopiomelanocortin gene transcript and two endogenous antagonists, agouti and agouti-related protein (AGRP). The key binding and functional determinant of AGRP, an MC3R and MC4R antagonist, is an Arg-Phe-Phe tripeptide sequence located on an exposed hexapeptide (Arg-Phe-Phe-Asn-Ala-Phe) loop. It has previously been observed that cyclizing this sequence through a DPro-Pro motif (c[Pro¹-Arg²-Phe³-Phe⁴-Asn⁵-Ala⁶-Phe⁷-DPro⁸]) resulted in a macrocyclic scaffold with MC4R antagonist activity, with increased MC4R potency when a diaminopropionic acid (Dap) residue is substituted at positio

SUBMITTER: Ericson MD 

PROVIDER: S-EPMC7549258 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature