Structure-activity relationship of uniconazole, a potent inhibitor of ABA 8'-hydroxylase, with a focus on hydrophilic functional groups and conformation.
The plant growth retardant S-(+)-uniconazole (UNI-OH) is a strong inhibitor of abscisic acid (ABA) 8'-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, stomatal closure, flowering, seed dormancy, and other physiological events. In the present study, we focused on the two polar sites of UNI-OH and synthesized 3- and 2''-modified analogs. Conformational analysis and an in vitro enzyme inhibition assay yielded new findings on the structure-activity relationship of UNI-OH: (1) by substituting imidazole for triazole, which increases affinity to heme iron, we identified a more potent compound, IMI-OH; (2) the polar group at the 3-position increases affinity for the active site by electrostatic or hydrogen-bonding interactions; (3) the conformer preference for a polar environment partially contributes to affinity for the active site. These findings should be useful for designing potent azole-containing specific inhibitors of ABA 8'-hydroxylase.
Todoroki
Yasushi
Y
Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka 422-8529, Japan. aytodor@agr.shizuoka.ac.jp
Kobayashi
Kyotaro
K
Yoneyama
Hidetaka
H
Hiramatsu
Saori
S
Jin
Mei-Hong
MH
Watanabe
Bunta
B
Mizutani
Masaharu
M
Hirai
Nobuhiro
N
D001665:Binding Sites; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D010940:Plant Proteins; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D010940:Plant Proteins; D014230:Triazoles; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C107203:abscisic acid 8'-hydroxylase; C092705:uniconazole