Development of macrocylclic peptide drug that targets membrane proteins using cultivated human cell lines

2014 Fiscal Year Final Research Report

• Project/Area Number: 24681047
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Chemical biology
• Research Institution: The University of Tokyo
• Principal Investigator: KATOH Takayuki 東京大学, 理学(系)研究科(研究院), 助教 (90567760)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 膜タンパク質 / ペプチド医薬 / RaPIDディスプレイ / 翻訳 / 遺伝暗号リプログラミング / アゴニスト

Outline of Final Research Achievements

In this research project, we developed a new method for screening non-standard macrocyclic peptide drugs that target cell-surface molecules such as membrane proteins. Normally, target molecules need to be immobilized on magnetic beads for applying in-vitro display method combined with random peptide library. However, immobilization of membrane proteins is generally difficult because isolation and solubilization of such proteins are impossible in many cases. Therefore, in this project, we developed a new in-vitro display method that utilizes cultured cells and/or baculovirus expressing membrane proteins on their surface instead of purified proteins immobilized on beads. By using this method, we could successfully obtain macrocyclic peptides that target CD20, IL28RA, Claudin-1 and 4.

Free Research Field

分子生物学