antinematodal activities of rare sugars

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Kagawa University
• Principal Investigator: Sato Masashi 香川大学, 農学部, 教授 (20263890)
• Co-Investigator(Kenkyū-buntansha): 吉原 明秀 香川大学, 農学部, 准教授 (40548765)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 希少糖 / D-アラビノース / 線虫 / Caenorhabditis elegans

Outline of Final Research Achievements

We have reported that the rare sugar, D-arabinose (D-Ara), a stereoisomer of D-ribose, inhibits the growth of the nematode Caenorhabditis elegans. However, the underlying mechanism of action is unclear. D-Ara is presumed to be phosphorylated by sugar kinases to yield D-Ara-5-phosphate (D-Ara-5P), which inhibits enzymes involved in sugar metabolism. We focused on two enzymes as targets for D-Ara-5P, i.e. glucose phosphate isomerase (GPI) in glycolysis, and ribose phosphate isomerase (RPI) in the pentose phosphate pathway. D-Ara-5P showed inhibitory activities against both C. elegans enzymes, which may account for the D-Ara-mediated growth inhibition.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

単糖を抗線虫薬（あるいはそのリード化合物）とした研究例は皆無であり，独創性が高い。本研究により，糖代謝をターゲットとした新規な作用メカニズムをもつ抗線虫薬の開発が期待でき，熱帯医学，獣医学への波及効果が大きいと考えられる。また，本研究で得られる知見から，抗がん剤などの他の薬剤，あるいは糖代謝酵素の機能を解析するツールとしての酵素阻害剤が開発される可能性がある。