Fluorescent Inhibitors of Thymidylate Synthetase

• Published in: Journal of pharmaceutical sciences 1977-03, Vol.66 (3), p.434-436
• Main Authors: Deits, Thomas L., Gapski, George R., Whiteley, John M.
• Format: Article
• Language: English
• Subjects: 2′-Deoxy- 5-fluorouridylate ester—fluorescent derivatives synthesized inhibition of thymidylate synthetase evaluated; 2′-Deoxy-5-fluorouridylate ester-fluorescent derivatives synthesized; effect on thymidylate synthetase; Enzyme inhibitors-fluorescent derivatives of 2′-deoxy-5-fluorouridylate ester synthesized; Enzyme inhibitors—fluorescent derivatives of 2'-deoxy-5-fluorouridylate ester synthesized effect on thymidylate synthetase; Fluoresceins - chemical synthesis; Fluoresceins - pharmacology; Fluorescence; Fluorodeoxyuridylate - analogs & derivatives; Fluorodeoxyuridylate - chemical synthesis; Fluorodeoxyuridylate - pharmacology; inhibition of thymidylate synthetase evaluated; Lactobacillus casei - enzymology; Methods; Methyltransferases - antagonists & inhibitors; Naphthalenes - chemical synthesis; Naphthalenes - pharmacology; Thymidylate Synthase - antagonists & inhibitors; Thymidylate synthetase-inhibition by fluorescent derivatives of 2′-deoxy-5-fluorouridylate ester evaluated; Uracil Nucleotides - chemical synthesis
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600660334

Two fluorescent derivatives of 2'-deoxy-5-fluorouridine 5'-p-aminophenyl phosphate were prepared by treatment of this compound with fluorescein isothiocyanate in dimethyl sulfoxide or 5-(di- methylamino)naphthalenesulfonyl chloride in pyridine. The products of the reactions were isolated by diethylaminoethylcellulose chromatography and were shown to be homogeneous by polyacrylamide electrophoresis and TLC. Confirmation of the structure was provided by elemental analysis, absorption and fluorescence spectra, PMR measurements, and liberation of nucleotide upon hydrolysis with snake venom phosphodiesterase. The fluorescent derivatives are good com-