Discovery of a follistatin-derived myostatin inhibitory peptide

Mariko Saitoh; Kentaro Takayama; Keisuke Hitachi; Akihiro Taguchi; Atsuhiko Taniguchi; Kunihiro Tsuchida; Yoshio Hayashi

doi:10.1016/j.bmcl.2019.126892

Discovery of a follistatin-derived myostatin inhibitory peptide

Mariko Saitoh, Kentaro Takayama, Keisuke Hitachi, Akihiro Taguchi, Atsuhiko Taniguchi, Kunihiro Tsuchida, Yoshio Hayashi

Division for Therapies against Intractable Diseases

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Abstract

Follistatin is well known as an inhibitor of transforming growth factor (TGF)-β superfamily ligands including myostatin and activin A. Myostatin, a negative regulator of muscle growth, is a promising target with which to treat muscle atrophic diseases. Here, we focused on the N-terminal domain (ND) of follistatin (Fst) that interacts with the type I receptor binding site of myostatin. Through bioassay of synthetic ND-derived fragment peptides, we identified DF-3, a new myostatin inhibitory 14-mer peptide which effectively inhibits myostatin, but fails to inhibit activin A or TGF-β1, in an in vitro luciferase reporter assay. Injected intramuscularly, DF-3 significantly increases skeletal muscle mass in mice and consequently, it can serve as a platform for development of muscle enhancement based on myostatin inhibition.

Original language	English
Article number	126892
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2019.126892
Publication status	Published - 01-02-2020

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All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Cite this

Saitoh, M., Takayama, K., Hitachi, K., Taguchi, A., Taniguchi, A., Tsuchida, K., & Hayashi, Y. (2020). Discovery of a follistatin-derived myostatin inhibitory peptide. Bioorganic and Medicinal Chemistry Letters, 30(3), [126892]. https://doi.org/10.1016/j.bmcl.2019.126892

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AU - Tsuchida, Kunihiro

AU - Hayashi, Yoshio

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10.1016/j.bmcl.2019.126892