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ID: ALA4725299

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of peptidic partial agonists of human neuromedin U receptor 1 with enhanced serum stability.

Authors: Takayama K,Mori K,Asari T,Sohma Y,Nomura E,Sasaki Y,Taguchi A,Taniguchi A,Miyazato M,Minamino N,Kangawa K,Hayashi Y

Abstract: Neuromedin U (NMU) activates two receptors (NMUR1 and NMUR2) and is a promising candidate for development of drugs to combat obesity. Previously, we obtained hexapeptides as selective full NMUR agonists. Development of a partial agonist which mildly activates receptors is an effective strategy which lead to an understanding of the functions of NMU receptors. In 2014, we reported hexapeptide 3 (CPN-124) as an NMUR1-selective partial agonist but its selectivity and serum stability were unsatisfactory. Herein, we report the development of a hexapeptide-type partial agonist (8, CPN-223) based on a peptide (3) but with higher NMUR1-selectivity and enhanced serum stability. A structure-activity relationship study of synthetic pentapeptide derivatives suggested that a hexapeptide is a minimum structure consistent with both good NMUR1-selective agonistic activity and serum stability.

CiteXplore: 32721452

DOI: 10.1016/j.bmcl.2020.127436