Phosphorylation of the anti-HIV compound (S,S)-isodideoxyadenosine by human recombinant deoxycytidine kinase.
Phosphorylation of the anti-HIV compound (S,S)-isodideoxyadenosine by human recombinant deoxycytidine kinase.
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DOI：
10.1016/s0006-2952(00)00462-7
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发表时间：
2000-11
影响因子：
5.8
通讯作者：
S. Pal;V. Nair
中科院分区：
文献类型：
--
作者：
S. Pal;V. Nair
(S,S)-Isodideoxyadenosine [(S,S)-isoddA] is an anti-HIV active compound discovered in our laboratory. However, its cellular mechanism of action, particularly the critical first stage of phosphorylation, is not understood. IsoddA is not phosphorylated by adenosine kinase. Also, because it is not a substrate for adenosine deaminase, it would not be activated by the pathway taken by ddA, i.e. via 5′-nucleotidase phosphorylation of ddI and conversion of ddIMP to ddAMP. However, we have discovered that human recombinant 2′-deoxycytidine kinase (dCK) phosphorylates (S,S)-isoddA. The enzyme kinetic data revealed that the extent of monophosphorylation of this l-related nucleoside was comparable to that found with ddA. (S,S)-IsoddATP is among the most potent inhibitors of HIV reverse transcriptase known, which suggests that the observed low efficiency of phosphorylation of this compound by dCK is a key factor that limits the capacity of human lymphocytes to make (S,S)-isoddA an exceptionally active anti-HIV agent.
