45. Uniconazoleの立体配座とABA 8'-hydroxylase阻害活性の関係(口頭発表)

概要

論文の詳細を見る
Uniconazole, which is well known as a triazole-containing inhibitor of ent-kaurene oxidase, functions as a very strong inhibitor of ABA 8'-hydroxylase. Azole-containing P450 inhibitors bind to a P450 active site by both coordinating to the heme-iron atom via sp^2 nitrogen and interacting with the surrounding protein residues through the lipophilic region. Because the heme coordination results from the intrinsic affinity of the ligand nitrogen electron pair for the heme iron, the P450 isoform selectivity should depend on the steric interaction with active site. For developing a specific inhibitor of ABA 8'-hydroxylase, we focused on the conformational profile of uniconazole. The NMR, X-ray crystallography and theoretical analyses revealed that the SD-structure of uniconazole is strongly affected by the hydrogen-bonding interaction between the 3-hydroxyl group and triazole 2"-nitrogen. We synthesized the uniconazole analogs that were modified at C3 and N2"and examined their inhibitory activity against ABA 8'-hydroxylase. The data obtained in this study suggest that the control of azole ring rotation may be a key for developing the specific inhibitor against plant P450.
2007-10-05