Thymidine 5 -phosphate, complex with

The kinase which converts deoxycytidine to its 5 -monophosphate has been studied most extensively in preparations from calf thymus 35, 36). The preferred substrate is deoxycytidine, for which the Michaelis constant (5 X 10 M) is much lower than that of two other substrates, deoxyadenosine and deoxyguanosine. Cytidine, uridine, and thymidine are not phosphorylated by this enzyme. Deoxycytidine kinase is subject to a complex pattern of allosteric regulation by nucleotides. The end product of deoxycytidine phosphorylation, dCTP, is a potent inhibitor this inhibition is reversed by dTTP. The enzyme has a rather broad specificity for the phosphate donor, with the triphosphates of the natural ribo- and deoxyribonucleosides being substrates the inactivity of dCTP is a notable exception. 

This enzyme [EC 2.7.1.21], better known as thymidine kinase, catalyzes the reaction of ATP with thymidine to produce ADP and thymidine 5 -phosphate. Deoxyuri-dtne can serve as a substrate and dGTP can substitute for ATP. The deoxypyrimidine kinase complex induced by herpes simplex virus catalyzes this reaction as well as those of AMPithymidine kinase, ADPithymidine kinase, and dTMP kinase. 

Figure 12-29 Drawing showing the hydrogen-bonding interactions between the guanidinium ions of arginines 35 and 87 of the micrococcal (staphylococcal) nuclease with the 5 -phosphate of the inhibitor thymidine 3, 5 -diphosphate in the complex of E + I + Ca2+. A possible mechanism is illustrated. A hydroxyl ion bound to Ca2+ carries out an in-line attack on the phosphorus. See Libson et al.S26...

Nucleotide bases (Fig. 7.16) have been derivatized by use of electrophilic organoiron complexes. The carbonyliron adducts 37 and 38 are typical examples [98]. A recent development in this field has led to the synthesis [99] of an extensive set of stmctures, including 39 which more closely resembles a nucleoside. The thymidine derivative 40 is an inhibitor of human thymidine kinase [100]. In the case of 41, the carbonylmetal component is attached at the heterocyclic base [101]. The carbonylmetal component can also be attached to dinucleotides by coordination at a phosphite, placed (as in 42) where the phosphate link would normally join the ribose rings [102]. The attachment of carbonylmetal labels to oligonucleotides for analysis by FTIR has also been described. The succini-midyl-based delivery strategy is the same as that used with proteins, as a... 

DEAE-cellulose has been reported to undergo irreversible binding, via a base-pairing mechanism, with poly(vinyl alcohol) substituted with oligo(deoxy-thymidine 5 -phosphate). It was possible to separate mixtures of synthetic oligonucleotides using the complexed cellulose derivative as an aflSnity-chromatography matrix. 

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