45.ジベレリン生合成酵素選択的P450阻害剤のスクリーニング(口頭発表)

概要

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Gibberellins (GAs) are plant hormone involved in stem elongation, seed germination, induction of flowering and other physiological events. Uniconazole (UNI), which is well known as a triazole-containing inhibitor of GA biosynthetic enzyme (CYP701A), functions as an inhibitor of multiple P450 enzymes including ABA 8'-hydroxylase (CYP707A), which is a key enzyme for ABA catabolism. We speculated that low selectivity of UNI may be resulted from its small and flexible conformation adjustable for variety of substrate pockets. Based on this speculation, we developed UNI analogues which is conformationally restricted (Abscinazole-F1), enlarged (-E1), disubstituted with azole (-D1), as specific inhibitors of CYP707A. We examined their inhibitory activity against recombinant CYP707A and the growth of rice seedlings, which is regulated by GA. However, because the growth of rice seedlings is also regulated by other plant hormones, the inhibitory activity is not fully equivalent to inhibitory activity against GA biosynthetic P450s. Thus we constructed an assay system of CYP701A inhibition using recombinant rice CYP701 As. We are performing in vitro screening of azole compound libraries using this system to find a selective inhibitor for CYP701A.
2010-10-01