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ID: ALA4396903

Journal: ACS Med Chem Lett

Title: Chain-Shortened Myostatin Inhibitory Peptides Improve Grip Strength in Mice.

Authors: Takayama K, Asari T, Saitoh M, Nirasawa K, Sasaki E, Roppongi Y, Nakamura A, Saga Y, Shimada T, Ikeyama H, Taguchi A, Taniguchi A, Negishi Y, Hayashi Y.

Abstract: Inhibition of myostatin is a promising strategy for treatment of muscle atrophic disorders. We had already identified a 23-mer peptide (1) as a synthetic myostatin inhibitor, and structure-activity relationship studies with 1 afforded a potent 22-mer peptide derivative (3). Herein, we report the shortest myostatin inhibitory peptide so far. Among chain-shortened 16-mer peptidic inhibitors derived from the C-terminal region of 3, peptide inhibitor 8a with β-sheet propensity was twice as potent as 22-mer inhibitor 3 and significantly increased not only muscle mass but also hind limb grip strength in Duchenne muscular dystrophic model mice. These results suggest that 8a is a promising platform for drug development treating muscle atrophic disorders.

CiteXplore: 31223459

DOI: 10.1021/acsmedchemlett.9b00174