Toward overcoming drug resistance problem: Development of a novel system to evaluate inhibitor that interacts with protein backbone through hydrogen bonding

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K15712
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Shizuoka University
• Principal Investigator: Sato Kohei 静岡大学, 工学部, 助教 (30756705)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 難溶性ペプチド / タンパク質化学合成 / 水溶性タグ / HIV-1プロテアーゼ / ヒドラジド

Outline of Final Research Achievements

In the field of treatment of viral infections, strategies for drug discovery are required to prevent the acquisition of drug resistance. Developing enzyme inhibitors that use hydrogen bonding with the protein backbones as a driving force is a practical approach to this problem. To establish an evaluation system of such types of inhibitors, a protein probe incorporating multiple isotopes labelling in a site-specific manner is essential, and the preparation of protein probes by chemical synthesis is required. In this study, we developed an efficient synthetic method for HIV-1 protease, one of the target enzymes of anti-HIV drugs.

Free Research Field

ペプチド化学、タンパク質化学

Academic Significance and Societal Importance of the Research Achievements

特殊な修飾をもつタンパク質をつくる技術として、化学合成法が利用される。多くのタンパク質が化学的に合成されてきたが、原料や合成中間体が溶けない場合には合成を先に進めることが難しくなる。今回HIV-1プロテアーゼの化学合成を進める中で溶解性の問題に直面し、これを解決する新しい可溶化技術の開発に成功した。本技術は、HIV-1プロテアーゼに限らず溶解性が問題となる幅広いタンパク質合成に応用可能であり、これまで合成困難と考えられてきたタンパク質の化学合成を可能にする。