Chiral inversion of 1-hydroxyethylpyrene enantiomers mediated by enantioselective sulfotransferases.
The benzylic alcohol 1-hydroxyethylpyrene (1-HEP) is activated to a mutagen by sulfotransferases. The sulfuric acid ester formed is difficult to detect, as it is rapidly hydrolysed back to the alcohol. Incubation of the individual enantiomers of 1-HEP with human hydroxysteroid sulfotransferase (hHST) or estrogen sulfotransferase (hEST), expressed in bacteria, led to the formation of the other enantiomer. The rates of sulfation were determined from the initial rates of chiral inversion of the alcohol, knowing that hydrolysis follows an SN1 mechanism and therefore produces racemic alcohol. hEST showed high enantioselectivity for S-1-HEP, whereas hHST strongly preferred the R-enantiomer. The rates of sulfation of the preferred enantiomers were high, similar to those for the prototype substrates of hEST (beta-estradiol) and hHST (dehydroepiandrosterone). Moreover, after a 30-min incubation of S-1-HEP with hEST, 95% of the recovered alcohol showed the R-configuration, indicating that several cycles of sulfation and hydrolysis had led to the depletion of one enantiomer and to the enrichment of the other enantiomer.
Landsiedel
R
R
German Institute of Human Nutrition (DIfE), Department of Toxicology, Potsdam-Rehbruecke, Germany.
Pabel
U
U
Engst
W
W
Ploschke
J
J
Seidel
A
A
Glatt
H
H
D001592:Benzyl Alcohols / Q000737:chemistry*; D006801:Humans; D010724:Phosphoadenosine Phosphosulfate / Q000737:chemistry; D012486:Salmonella typhimurium / Q000201:enzymology; D013237:Stereoisomerism; D015238:Sulfotransferases / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000737:chemistry
D001592:Benzyl Alcohols; D013463:Sulfuric Acid Esters; D010724:Phosphoadenosine Phosphosulfate; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; C020122:estrone sulfotransferase