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.
School of Chemical Sciences, The University of Birmingham, Edgbaston, UK.
Rakesh S
RS
Bargota
Mahmoud
M
Akhtar
Keith
K
Biggadike
David
D
Gani
Rudolf K
RK
Allemann
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