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

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

16 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
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

Access to Document

10.1016/j.bmcl.2019.126892

Cite this

@article{2997e7810106472ebd7237545db5a6c4,

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.",

keywords = "Follistatin, Inhibitor, Muscle mass enhancer, Myostatin, Synthetic peptide",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2020",

month = feb,

day = "1",

doi = "10.1016/j.bmcl.2019.126892",

language = "English",

volume = "30",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "3",

}

TY - JOUR

T1 - Discovery of a follistatin-derived myostatin inhibitory peptide

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

UR - http://www.scopus.com/inward/record.url?scp=85076985266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076985266&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.126892

DO - 10.1016/j.bmcl.2019.126892

M3 - Article

C2 - 31874826

AN - SCOPUS:85076985266

SN - 0960-894X

VL - 30

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

M1 - 126892

ER -

Discovery of a follistatin-derived myostatin inhibitory peptide

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this