A new non-azole inhibitor of ABA 8'-hydroxylase: effect of the hydroxyl group substituted for geminal methyl groups in the six-membered ring.
We designed and synthesized AHI4 that has an axial hydroxyl group instead of geminal methyl groups at C-6' of AHI1, previously reported as a lead compound for the development of non-azole inhibitors of ABA 8'-hydroxylase. (+)-AHI4 competitively inhibited 8'-hydroxylation of ABA by recombinant CYP707A3. The K(I) value was found to be 0.14 microM, 10-fold less than that of (+)-AHI1, suggesting that enzyme affinity increased by a factor of 10 due to substitution of the hydroxyl group by the geminal methyls at C-6'. This finding should assist in the design of more effective, non-azole ABA 8'-hydroxylase inhibitors.
Araki
Yoshiharu
Y
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka 422-8529, Japan.
Miyawaki
Arisa
A
Miyashita
Tomoyuki
T
Mizutani
Masaharu
M
Hirai
Nobuhiro
N
Todoroki
Yasushi
Y
D001393:Azoles / Q000737:chemistry / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006900:Hydroxylation; D008745:Methylation; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D012275:Oryza / Q000187:drug effects / Q000201:enzymology; D010940:Plant Proteins; D036226:Seedlings / Q000187:drug effects / Q000201:enzymology; D014867:Water
D001393:Azoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010940:Plant Proteins; D014867:Water; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C107203:abscisic acid 8'-hydroxylase