1. Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.
- Author
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Takayama K, Nakamura A, Rentier C, Mino Y, Asari T, Saga Y, Taguchi A, Yakushiji F, and Hayashi Y
- Subjects
- Acylation, Dose-Response Relationship, Drug, HEK293 Cells, Humans, Molecular Structure, Myostatin metabolism, Peptides chemical synthesis, Peptides chemistry, Structure-Activity Relationship, Myostatin antagonists & inhibitors, Peptides pharmacology
- 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 peptide 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 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 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
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