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

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmcl.2019.126892

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title = "Discovery of a follistatin-derived myostatin inhibitory peptide",

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.",

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author = "Mariko Saitoh and Kentaro Takayama and Keisuke Hitachi and Akihiro Taguchi and Atsuhiko Taniguchi and Kunihiro Tsuchida and Yoshio Hayashi",

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AU - Saitoh, Mariko

AU - Takayama, Kentaro

AU - Hitachi, Keisuke

AU - Taguchi, Akihiro

AU - Taniguchi, Atsuhiko

AU - Tsuchida, Kunihiro

AU - Hayashi, Yoshio

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

KW - Follistatin

KW - Inhibitor

KW - Muscle mass enhancer

KW - Myostatin

KW - Synthetic peptide

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ER -

Discovery of a follistatin-derived myostatin inhibitory peptide

Abstract

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