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
N1 - Funding Information:
This research was supported by JSPS KAKENHI 17K15484 (K.Takayama), AMED under Grant Number A257TS (Y.H.), MEXT -supported Program for the Strategic Research Foundation at Private Universities (Y.H.), and Intramural Research Grant (29-4) for Neurological and Psychiatric Disorders on NCNP (K. Tsuchida and Y.H.). The authors thank Ms. Akari Nakamura for supports of peptide synthesis and cell-based assay. Appendix A
Funding Information:
This research was supported by JSPS KAKENHI17K15484 (K.Takayama), AMED under Grant Number A257TS (Y.H.), MEXT-supported Program for the Strategic Research Foundation at Private Universities (Y.H.), and Intramural Research Grant (29-4) for Neurological and Psychiatric Disorders on NCNP (K. Tsuchida and Y.H.). The authors thank Ms. Akari Nakamura for supports of peptide synthesis and cell-based assay.
Publisher Copyright:
© 2019 Elsevier Ltd
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.
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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 -