Structure-activity relationship on human serum paraoxonase (PON1) using substrate analogues and inhibitors.
Substrate analogues based on the parent compounds paraoxon and phenyl acetate were tested on human serum paraoxonase (PON1) to explore the active site of the enzyme. Replacement of the nitro group of paraoxon with an amine or hydrogen, as well as electronic changes to the parent compound, converted these analogues into inhibitors. Introduction of either electron-withdrawing or donating groups onto phenyl acetate resulted in reduction in their rate of hydrolysis by PON1.
Bargota
Rakesh S
RS
School of Chemical Sciences, The University of Birmingham, Edgbaston, UK.
Akhtar
Mahmoud
M
Biggadike
Keith
K
Gani
David
D
Allemann
Rudolf K
RK
D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010261:Paraoxon / Q000031:analogs & derivatives / Q000737:chemistry; D010648:Phenylacetates / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D010648:Phenylacetates; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C025136:phenylacetic acid; D010261:Paraoxon