Fluorescent inhibitors of thymidylate synthetase.
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-(dimethylamino)naphthalene sulfonyl 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 competitive inhibitors (Ki approximately10(-6) M) of thymidylate synthetase from a methotrexate-resistant strain of Lactobacillus casei.
D005452:Fluoresceins / Q000138:chemical synthesis / Q000494:pharmacology; D005453:Fluorescence; D005468:Fluorodeoxyuridylate / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D007780:Lacticaseibacillus casei / Q000201:enzymology; D008722:Methods; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014500:Uracil Nucleotides / Q000138:chemical synthesis*
D005452:Fluoresceins; D009281:Naphthalenes; D014500:Uracil Nucleotides; D005468:Fluorodeoxyuridylate; D008780:Methyltransferases; D013940:Thymidylate Synthase