Chain-Shortened Myostatin Inhibitory Peptides Improve Grip Strength in Mice

Abstract

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