Development of Potent Myostatin Inhibitory Peptides through Hydrophobic Residue-Directed Structural Modification.

ABSTRACT: Myostatin, a negative regulator of skeletal muscle growth, is a promising target for treating muscle atrophic disorders. Recently, we discovered a minimal myostatin inhibitor 1 (WRQNTRYSRIEAIKIQILSKLRL-amide) derived from positions 21-43 of the mouse myostatin prodomain. We previously identified key residues (N-terminal Trp²¹, rodent-specific Tyr²⁷, and all aliphatic amino acids) required for effective inhibition through structure-activity relationship (SAR) studies based on 1 and characterized a 3-fold more potent inhibitor 2 bearing a 2-naphthyloxyacetyl group at position 21. Herein, we performed 1-based SAR studies focused on all aliphatic residues and Ala³², discovering that the incorporations of Trp and Ile at positions 32 a

SUBMITTER: Takayama K 

PROVIDER: S-EPMC5512132 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature