Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.
ChemMedChem
; 11(8): 845-9, 2016 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-26954624
ABSTRACT
Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptideâ
A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptideâ
A was successfully identified in which the N-terminal tryptophan residue is replaced with a 2-naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11â
µm) more potent than parent peptideâ
A (3.53±0.25â
µm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Miostatina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article