Generation of peptide-based drugs for muscular dystrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K13741
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry
• Research Institution: Kyoto University
• Principal Investigator: Hara Yuji 京都大学, 工学研究科, 准教授 (60362456)
• Co-Investigator(Renkei-kenkyūsha): UMEDA Masato 京都大学, 大学院工学研究科, 教授 (10185069) ; Nagao Kohjiro 京都大学, 大学院工学研究科, 助教 (40587325)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 筋ジストロフィー / ペプチド医薬 / 糖鎖修飾

Outline of Final Research Achievements

Dystroglycan is a membrane protein that bears phosphorylated O-mannosyl glycans. Impaired glycosylation of dystroglycan causes muscular dystrophy due to a lack of the interactin with laminin, one of the major constituents of extracellular matrix. To develop the probe that can detect hypo-glycosylated forms on dystroglycan, we utilized a multivalent peptide library that contains randomized amino acid sequences. We focused on a phosphate residue on O-mannosyl glycan because of its importance for the interaction with laminin. This attempt identified a specific amino acid sequence composed of a series of basic amino acid residues but contained tryptophan residues. This result suggests that not only electrostatic interaction but also specificity of amino acid sequences would be crucial for the interaction between dystorlgycan's glycans and laminin.

Free Research Field

筋細胞生物学