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 peptideA (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 peptideA 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 +/- 0.11m) more potent than parent peptideA (3.53 +/- 0.25m). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides.