5'-Substituted 2'-Deoxycytidines as Non-Substrate Inhibitors of Human Deoxycytidine Kinase

Abstract
Several 5′-substituted analogues of 2′-deoxycytidine (dC), including 5′-amino2′,5′-dideoxycytidine (5′-amino-ddC), 5′-azido-2′,5′-dideoxycytidine (5′-azido-ddC) and 5′-O-ethyl-2′-deoxycytidine (5′-O-ethyl-dC), are non-substrate inhibitors of human dC kinase. Whereas 5′-amino-ddC inhibits phosphorylation of deoxyadenosine (dA) with Ki ∼ 1 μ inhibition of phosphorylation of dC is bimodal and more effective at low inhibitor concentrations. In particular 5′-O-ethyl-dC inhibits phosphorylation of dA 10-fold more effectively (Ki ∼ 3 μ) than that of dC (Ki ∼ 30 μ). For 5′-azido-ddC inhibition was shown directly to be competitive with respect to substrate.

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