Abstract
CYP701A, a gibberellin (GA) biosynthetic P450 enzyme, catalyzes the three step oxidation of ent-kaurene to ent-kaurenoic acid. A selective inhibitor of this enzyme is a promising research tool for chemical genetic studies of GA deficiency. Uniconazole (UNI), paclobutrazol (PAC), inabenfide (IBF) and ancymidol (ANC) have been known as inhibitors of CYP701A. Although their selectivity has little been investigated biochemically, recent researches suggest that UNI, PAC, and ANC are not specific to CYP701A; UNI and PAC act as an inhibitor of CYP707A, a catabolic enzyme of abscisic acid, and ANC inhibits cellulose synthesis. Hence, we launched the development of a novel selective inhibitor of CYP701A. Recently we developed a selective and potent inhibitor of CYP707A, abscinazoles, by screening our library of UNI analogues whose structures are enlarged or conformationally restricted to eliminate structural factors that may cause the low enzyme selectivity. This library may contain a selective inhibitor of CYP701A. We examined inhibitory activities of compounds in the library against recombinant rice CYP701A6 and Arabidopsis CYP707A3 enzymes. Finally we found a conformationally restricted UNI analogue, UFAP2, that strongly inhibited CYP701A6 without exhibiting considerable inhibitory effect on CYP707A3. Here we present the enzyme selectivity, biological activity and water solubility of UFAP2 in comparison with those of other known CYP701A inhibitors.
