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Development of anti-multidrug resistant HIV drugs by structural chemical approach

Research Project

Project/Area Number 15K07898
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionIwaki Meisei University

Principal Investigator

TSUNODA Masaru  いわき明星大学, 薬学部, 准教授 (10347974)

Co-Investigator(Kenkyū-buntansha) 鈴木 薫  いわき明星大学, 薬学部, 客員研究員 (90382788)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗HIV薬 / タンパク質 / レクチン / アクチノヒビン / X線結晶構造解析 / HIV感染予防 / X線結晶構造解析 / HIV感染予防
Outline of Final Research Achievements

We used X-ray crystallography to analyze the crystal of the complex of HIV coat protein as an objective to establish a structural basis to improve a new lectin (actinohivin) that prevents HIV from infecting human cells and has a mechanism of action that does not develop drug resistance as a more effective novel HIV infection prevention agent.
The three-dimensional structure of actinohivin forms a cyclic structure in which three segments are arranged symmetrically, and it has become clear that each has a pocket that binds to a sugar chain. Since one high-mannose type sugar chain is bound to each pocket, three sugar chains are simultaneously bound, and the binding of actinohivin to the HIV coat protein was considered to be quite specific and strong.

Academic Significance and Societal Importance of the Research Achievements

HIVがヒト細胞へ感染することを阻止し、さらに薬剤耐性を発症しない作用機構を持った、新しいレクチン(アクチノヒビンと命名)をより効果的な新しいHIV感染予防薬として改良するための構造基板を確立することを目的に、X線結晶構造解析を進め、アクチノヒビンとHIV外套糖タンパク質との複合体の結晶解析に取り組んだ。
その結果、HIV表面を覆う糖タンパク質から突き出た高マンノースの先端部位にある糖との複合体の構造解析から、AHと糖鎖との結合様式を確認することができた。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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