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 journalArticle

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 languageEnglish
Article number126892
JournalBioorganic and Medicinal Chemistry Letters
Volume30
Issue number3
DOIs
Publication statusPublished - 01-02-2020

Fingerprint

Myostatin
Follistatin
Peptides
Muscle
Transforming Growth Factors
Muscles
Peptide Fragments
Muscle Development
Bioassay
Luciferases
Biological Assay
Assays
Skeletal Muscle
Binding Sites
Ligands
Growth

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
Saitoh, Mariko ; Takayama, Kentaro ; Hitachi, Keisuke ; Taguchi, Akihiro ; Taniguchi, Atsuhiko ; Tsuchida, Kunihiro ; Hayashi, Yoshio. / Discovery of a follistatin-derived myostatin inhibitory peptide. In: Bioorganic and Medicinal Chemistry Letters. 2020 ; Vol. 30, No. 3.
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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, vol. 30, no. 3, 126892. https://doi.org/10.1016/j.bmcl.2019.126892

Discovery of a follistatin-derived myostatin inhibitory peptide. / Saitoh, Mariko; Takayama, Kentaro; Hitachi, Keisuke; Taguchi, Akihiro; Taniguchi, Atsuhiko; Tsuchida, Kunihiro; Hayashi, Yoshio.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 30, No. 3, 126892, 01.02.2020.

Research output: Contribution to journalArticle

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