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Effect of N‐Terminal Acylation on the Activity of Myostatin Inhibitory Peptides
Author(s) -
Takayama Kentaro,
Nakamura Akari,
Rentier Cédric,
Mino Yusaku,
Asari Tomo,
Saga Yusuke,
Taguchi Akihiro,
Yakushiji Fumika,
Hayashi Yoshio
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500533
Subject(s) - myostatin , peptide , residue (chemistry) , chemistry , serine , tryptophan , biochemistry , inhibitory postsynaptic potential , cysteine , acylation , amino acid , biology , endocrinology , enzyme , gene , catalysis
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 peptide A ( H‐WRQNTRYSRIEAIKIQILSKLRL‐NH 2 ), 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 peptide 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±0.11 μ m ) more potent than parent peptide A (3.53±0.25 μ m ). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides.