Identification of the minimum peptide from mouse myostatin prodomain for human myostatin inhibition

J Med Chem. 2015 Feb 12;58(3):1544-9. doi: 10.1021/jm501170d. Epub 2015 Jan 21.

Abstract

Myostatin, an endogenous negative regulator of skeletal muscle mass, is a therapeutic target for muscle atrophic disorders. Here, we identified minimum peptides 2 and 7 to effectively inhibit myostatin activity, which consist of 24 and 23 amino acids, respectively, derived from mouse myostatin prodomain. These peptides, which had the propensity to form α-helix structure, interacted to myostatin with KD values of 30-36 nM. Moreover, peptide 2 significantly increased muscle mass in Duchenne muscular dystrophy model mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Mice
  • Mice, Inbred mdx
  • Molecular Structure
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / metabolism
  • Myostatin / antagonists & inhibitors*
  • Myostatin / metabolism
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Structure-Activity Relationship

Substances

  • Myostatin
  • Peptides