title: Structural Basis for the Effective Myostatin Inhibition of the Mouse Myostatin Prodomain-Derived Minimum Peptide.
abstract: Myostatin inhibition is one of the promising strategies for treating muscle atrophic disorders, including muscular dystrophy. It is well-known that the myostatin prodomain derived from the myostatin precursor acts as an inhibitor of mature myostatin. In our previous study, myostatin inhibitory minimum peptide1(WRQNTRYSRIEAIKIQILSKLRL-amide) was discovered from the mouse myostatin prodomain. In the present study, alanine scanning of1demonstrated that the key amino acid residues for the effective inhibitory activity are rodent-specific Tyr and C-terminal aliphatic residues, in addition to N-terminal Trp residue. Subsequently, we designed five Pro-substituted peptides and examined the relationship between secondary structure and inhibitory activity. As a result, we found that Pro-substitutions of Ala or Gln residues around the center of1significantly decreased both α-helicity and inhibitory activity. These results suggested that an α-helical structure possessing hydrophobic faces formed around the C-terminus is important for inhibitory activity.
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Asari
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
keywords: inhibitor; myostatin; peptide; structure−activity relationship; α-Helix