Enzyme Inhibition by Phosphonate Analogues of dTTP
Ribonucleotide reductase (RR) (EC 188.8.131.52), deoxycytidylate deaminase (dCMP DA) (EC 184.108.40.206) and thymidine kinase (TK) (EC 220.127.116.11) are important enzymes for the production of thymidine nucleotides, and are subject to feedback regulation by dTTP. Analogues of dTTP which mimic this regulatory behaviour might be useful inhibitors of both the de novo and salvage pathways of thymidylate biosynthesis. We have prepared and tested three phosphonate analogues of dTTP, αβ-methylene-dTTP (αβ-CH2-dTTP), βγ -methylene-dTTP (βγ-CH2-dTTP) and αβ,βγ-dimethylene-dTTP (αβ, βγ-CH2-dTTP) for inhibitory activity against these enzymes from L1210 cells.
KeywordsThymidine Kinase Ribonucleotide Reductase Salvage Pathway Pyridoxal Phosphate Ammonium Sulphate Fraction
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