Inhibition of reverse transcriptase by tyrosinase generated quinones related to levodopa and dopamine.
Several derivatives of levodopa have been shown to be potent inhibitors of the sulfhydryl enzyme, RNA dependent DNA polymerase, reverse transcriptase (RT). In the presence of the polyphenol oxidase, tyrosinase, the inhibitory values were between 10(-6) M and 10(-5) M. Structure-activity studies revealed that active oxidation or reduction was necessary for this potent inhibitory response. Spectrophotometric analysis showed that the presence of both the quinone and quinol was required for maximum inhibitory activity. These data suggest that the common intermediate of oxidation of quinols or reduction of quinones (i.e., semiquinone) is the active species. The use of tyrosinase provides a convenient model for the detection of the actual inhibitory interaction of a free-radical (semiquinone) with a biologically important macromolecule, reverse transcriptase.
D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D004156:Catechol Oxidase / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011809:Quinones / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D011809:Quinones; D018894:Reverse Transcriptase Inhibitors; D007980:Levodopa; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D004298:Dopamine