55.クリック反応を利用した高選択性アゾール系P450阻害剤の創製と探索(口頭発表)

概要

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Uniconazole (UNI), which is well known as a plant growth regulator, is a triazole-containing inhibitor of GA biosynthetic enzyme (CYP701A). UNI is also an inhibitor for ABA metabolic enzyme (CYP707A) and BR biosynthetic enzyme (CYP90B). The substrate specificity of P450 depends on the distal helical region which is located far from the heme. Because UNI binds to the heme by coordinating the nitrogen atom to the heme-iron, the 4-chlorophenyl group may interact with this region. Therefore, the alteration of the 4-chlorophenyl group of UNI may cause an increase in the enzyme selectivity. We synthesized UNI analogues modified at the 4-chlorophenyl group by 'click' reaction, and tested their enzyme specificity. UNI analogues with the 4-azidophenyl group (UNI-azide), which was prepared for click reaction, showed equivalent activity to UNI in the recombinant CYP707A inhibition assay, whereas the inhibitory activity for rice seedling elongation was much lower than that of UNI. This suggests that the alteration of the 4-chlorophenyl group of UNI enhances the enzyme selectivity. Eight UNI analogues were synthesized by click reaction between UNI-azide and acetylene compounds in presence of Cu(I). We are examining their inhibitory activity for P450 enzymes and plant growth.
植物化学調節学会の論文
2008-10-06