Chain-Shortened Myostatin Inhibitory Peptides Improve Grip Strength in Mice

• Published in: ACS medicinal chemistry letters Vol. 10; no. 6; pp. 985 - 990
• Main Authors: Takayama, Kentaro, Asari, Tomo, Saitoh, Mariko, Nirasawa, Kei, Sasaki, Eri, Roppongi, Yoshimi, Nakamura, Akari, Saga, Yusuke, Shimada, Takahiro, Ikeyama, Hiroaki, Taguchi, Akihiro, Taniguchi, Atsuhiko, Negishi, Yoichi, Hayashi, Yoshio
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.06.2019; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; peptide; Inhibitor; structure−activity relationship; muscle atrophic disorder; myostatin; SKELETAL-MUSCLE MASS; PRODOMAIN; IDENTIFICATION; structure-activity relationship; FOLLISTATIN
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/acsmedchemlett.9b00174

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.