Separation of individual antiviral nucleotide prodrugs from synthetic mixtures using cross-reactivity of a molecularly imprinted stationary phase

2',3'-Dideoxynucleosides (ddNs) are among the most potent of nucleoside ana logues active against human immunodeficiency virus (HIV) in cell culture. d 4T (2',3'-dideoxy-2',3'-didehydrothymidine) is clinically effective acting through competitive inhibition of viral reverse transcriptase and/or incorp oration and subsequent chain termination of the growing viral chain. Activa tion occurs via intracellular conversion to the 5'-triphosphate, the kinase -mediated formation of the monophosphate being the rate-limiting step and, therefore, strategies to deliver the monophosphate have been sought. This s tudy uses a molecularly imprinted HPLC stationary phase to separate single diastereomers for a number of nucleoside monophosphates prodrugs from synth etic mixtures. The biological activity of some individual diastereomers are unknown and a need to efficiently separate them from synthetic mixtures, h as been identified. Due to cross-reactive affinity for the imprinted polyme r one imprinted stationary phase was used to isolate a single diastereomer from a range of prodrug synthetic mixtures. (C) 2001 Elsevier Science B.V. All rights reserved.