Takayama Kentaro, Noguchi Yuri, Aoki Shin, Takayama Shota, Yoshida Momoko, Asari Tomo, Yakushiji Fumika, Nishimatsu Shin-ichiro, Ohsawa Yutaka, Itoh Fumiko, Negishi Yoichi, Sunada Yoshihide, Hayashi Yoshio
Department of Medicinal Chemistry, ‡Laboratory of Cardiovascular Medicine, and §Department of Drug Delivery and Molecular Biopharmaceutics, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo192-0392, Japan.
J Med Chem. 2015 Feb 12;58(3):1544-9. doi: 10.1021/jm501170d. Epub 2015 Jan 21.
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.
肌肉生长抑制素是骨骼肌质量的内源性负调节因子，是肌肉萎缩性疾病的治疗靶点。在此，我们鉴定出最小肽2和肽7可有效抑制肌肉生长抑制素活性，它们分别由24个和23个氨基酸组成，源自小鼠肌肉生长抑制素前结构域。这些倾向于形成α-螺旋结构的肽与肌肉生长抑制素相互作用，解离常数（KD）值为30 - 36 nM。此外，肽2显著增加了杜兴氏肌营养不良模型小鼠的肌肉质量。
