Nonclassical Antimetabolites. XXV.¹ Inhibitors of Thymidine Kinase. I. A New Spectrophotometric Assay. Inhibition by Nucleoside Derivatives

Radiation-induced binding of 2,2,6,6-tetramethyl-1,4-piperidone-N-oxyl to thymidine in oxygen-free aqueous solutions. Isolation and characterization of the adducts

“…Extraction of the silica gel (~~0 . h ) with methanol (3 x 6 mL) provided 1 1.5 mg of a nucleoside which was characterized as 5-hydroxymethyl-2'-deoxyuridine (14) by comparison of its uv, 'H nmr, and FAB mass spectrometric features with those of the authentic sample (28).…”

“…The major degradation product was characterized as 5-hydroxymethyl-2'-deoxyuridine (14) by comparison of some of its spectroscopic features (uv, EI-ms, 'H and I3C nrnr) with those of the authentic sample synthesized according to Baker et al (28). A likely mechanism for its formation would involve a Cope rearrangement, which is characteristic of N-oxide type compounds (29).…”

A Continuous Spectrophotometric Assay for Thymidine and Deoxycytidine Kinases

“…In addition to the requirement for radioisotopes, the above methods require sampling and analysis of multiple single points per assay, and are tedious for kinetic studies and purification procedures. A coupled spectrophotometric assay measuring ADP production has been reported for Urd kinase (6) which should be applicable to purified TK and dCK, but is unsuitable for crude preparations which invariably contain some form of ATPase activity (7).…”

Synthesis and Reaction of Pyrimidine Nucleosides

“…(330b) S-Bromo(fluoro or iodo)-2',3'-0-isopropylideneuridine (120) also behaved in a similar fashion. Treatment of (120) in alkaline medium produced five products, (121 )- (124). (331) In these transformations, a participation of the 5/ -hydroxyl group may not be essential for the formation of all products.…”

“…l-Methyl-5-hydroxyuracil was rearranged in a similar manner. The mechanism operating in this transformation seemed to be that of a benzilic acid rearrangement as shown in the sequence (122)- (124), through the intermediate (122A), (122B), and (122C). (332) The formation of 5-hydroxyuridine from 5-bromouridine had been substantiated by the conversion of 5-bromouracil to 5-hydroxyuracil by mild base treatment.…”