Discovery of a follistatin-derived myostatin inhibitory peptide.
Activins
/ antagonists & inhibitors
Amino Acid Sequence
Animals
Binding Sites
Follistatin
/ chemistry
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal
/ drug effects
Myostatin
/ antagonists & inhibitors
Peptides
/ chemistry
Protein Binding
Structure-Activity Relationship
Transforming Growth Factor beta
/ antagonists & inhibitors
Follistatin
Inhibitor
Muscle mass enhancer
Myostatin
Synthetic peptide
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
01
11
2019
revised:
04
12
2019
accepted:
05
12
2019
pubmed:
26
12
2019
medline:
29
1
2021
entrez:
26
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31874826
pii: S0960-894X(19)30870-4
doi: 10.1016/j.bmcl.2019.126892
pii:
doi:
Substances chimiques
Follistatin
0
Myostatin
0
Peptides
0
Transforming Growth Factor beta
0
activin A
0
Activins
104625-48-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126892Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.