51(P-8) Acremonium sp.の生産する哺乳類のDNAポリメラーゼα選択的阻害剤、dehydroaltenusin(ポスター発表の部)

概要

論文の詳細を見る
Eukaryotic cells reportedly contain at least eleven types of DNA polymerase (pol α,β,γ,δ,ε,ζ,η,θ,κ,λ,μ), We screened natural compounds that selectively inhibit DNA polymerase α. The purpose was to use the compounds as tools and molecular probes to distinguish DNA polymerases and to clarify their biological and in vivo function. There have been no previous reports of inhibitors capable of distinguishing among pol α, δ and ε. We found an interesting inhibitor that influenced only the activity of mammalian pol α from a fungus (Acremonium sp.). The agent, which was determined to be dehydroaltenusin by spectrometric analyses, has been reported to be the inhibitor of myosin light chain kinase. Dehydroaltenusin did not affect the activities of the other replicative DNA polymerase such as δ and ε, respectively. This compound also showed no effect on pol α activity even from another vertebrate such as fish, although the amino acid sequences of both DNA polymerases are highly homologous. The agent must be able to determine small structural differences between mammalian and fish pol α. Kinetic analysis, gel mobility shift analysis and surface plasmon resonance sensor (BIAcore) analysis suggested that dehydroaltenusin interacted DNA binding site of p180 subunit of pol α. Dehydroaltenusin will be a key agent for analyzing both in vitro and in vivo function of pol α in more detail. Dehydroaltenusin could inhibit the cell proliferation of human gastric cell line, NUGC-3 by arresting the cells at early S-phase, and prevented the incorporation of [^3H]-thymidine into the cells, indicating that it blocks the primary step of in vivo DNA replication by inhibiting pol α. Therefore, the agent should also be considered as a group of potentially useful cancer chemotherapeutic agents.
天然有機化合物討論会の論文
2001-09-01

51(P-8) Acremonium sp.の生産する哺乳類のDNAポリメラーゼα選択的阻害剤、dehydroaltenusin(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク