A study of covalent modifier evaluation method using HDX

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05361
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: Itoh Toshimasa 昭和薬科大学, 薬学部, 教授 (80536110)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 水素-重水素交換反応 / 共有結合 / 医薬品開発

Outline of Final Research Achievements

Drugs bind to proteins and change their behaviour to produce a drug effect. The binding mode between a typical drug and its binding partner protein is reversible, but some drugs have irreversible binding properties through covalent bonds. Typical examples include aspirin and penicillin, and many important drugs. The development of covalent drugs has been difficult due to screening limitations, but this study proposes a simple method for extracting covalent candidate compounds by focusing on changes in protein fluctuations using hydrogen-deuterium exchange MS.

Free Research Field

医薬品化学

Academic Significance and Societal Importance of the Research Achievements

生体分子のタンパク質と乖離しない性質をもつ共有結合型の医薬品には，多くの重要な治療薬が存在する。しかし，これらは偶然の産物であり，意図して共有結合型として開発されたわけではない。今回の成果は共有結合する化合物に対し，タンパク質の振る舞いを変えられるかどうかを一般的な質量分析を用い簡便に評価できるものであり，積極的な共有結合型医薬品の開発に貢献できるものと期待される。