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

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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… Click to show full 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.

Keywords: grip strength; myostatin inhibitory; chain shortened

Journal Title: ACS medicinal chemistry letters
Year Published: 2019

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