Effect of N‐Terminal Acylation on the Activity of Myostatin Inhibitory Peptides

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.