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 | |
| 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
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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 journal › Article
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.
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
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
M1 - 126892
ER -