Rational design of synthetic mid-sized agents that disrupt protein-protein interactions

2015 Fiscal Year Final Research Report

• Project/Area Number: 25288076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Kyoto University
• Principal Investigator: Ohkanda Junko 京都大学, 化学研究所, 准教授 (50233052)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: たんぱく質間相互作用 / 阻害剤 / 化学プローブ / 中分子 / K-Ras / フシコクシン

Outline of Final Research Achievements

Protein-protein interactions (PPIs) play a central role in the signaling pathways that regulate many cellular functions including proliferation, differentiation, and cell death, and have emerged as a new potential clinical targets in the post-genome era. In this study, we aimed to develop a series of mid-sized molecules, of which the molecular size roughly ranges from 600 to 2,000, to recognize the large and flat interfaces and disrupt and detect intracellular PPIs. The cell-permeable bivalent inhibitors of K-Ras-PPIs and the natural product-based fluorescent probes that detect interactions of 14-3-3 and the phospholigands were designed and evaluated in vitro and in cells.

Free Research Field

生物有機化学