Regioselectivity of catechol O-methyltransferase. The effect of pH on the site of O-methylation of fluorinated norepinephrines.

摘要: Selectivity of catechol O-methyltransferase has been examined for the three ring-fluorinated norepinephrines to elucidate role acidity phenolic groups in their methylation. Substitution fluorine at 5-position norepinephrine reverses selectivity so that p-O-methylation predominates. The 5-fluoro substituent also causes pKa p-hydroxyl group decrease substantially. In contrast, 2- and 6-fluoronorepinephrines are methylated predominantly m-hydroxyl group. These results suggest a can play an important its ability be by O-methyltransferase. Percentages fluorinated derivatives increase with pH. This relative appears accompany ionization 8.6, 7.7, 7.9, 8.4 2-, 5-, 6-fluoro derivative, respectively. values same as or similar hydroxyl these substrates. 3,4-Dihydroxybenzyl alcohol derivative O-methylated form p- m-O-methyl products approximately 1:1 4:1 ratios, respectively, all pH values. Based on above results, catechol-binding site model is proposed which two substrates postulated equally spaced from methyl cosubstrate S-adenosylmethionine.