Nucleoside drugs

Pascolo E, Wenz C, Lingner J et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non- nucleosidic drug candidate. J.Biol.Chem. 2002 277 15566-15572. 

HPLC/UV and HPLC/MS Assay of New Chemical Entities — Nucleoside Drugs... 

Finally, transport can also be driven by the conversion of intracellular substrate to another chemical form. For example, in the case of nucleoside drugs, conversion to the corresponding nucleotides by appropriate kinases may be the limiting factor in cellular uptake and activation. The same principle applies to sulfation, glu euro nidation, prodrug activations, or other metabolic processes that provide a removal of the transported species from the transportable (free) internal pool. In some cases, transport is directly coupled to substrate modification, as in the uptake of sugars into bacterial cells by phosphoenolpyruvate (PEP)-coupled phosphorylation systems. 

Cells differ in their reliance on nucleoside uptake and salvage versus de novo biosynthetic pathways for normal growth, and, hence, they differ in their sensitivity to nucleoside drugs. Table 14.5 [adapted from Tables 1-4 in Cass (61)] lists some nucleoside drugs, diseases for which they have been used, and the transporters that recognize them. In addition to the es, ei, and N1-N5 nucleoside transporters, some nucleoside drugs also utilize nucleobase (NB) transporters. 

Nucleoside drug Clinical indication Transporter specificity ... 

Apart from the amantadines (section 14.1) and me-thisazone (section 14.2), various non-nucleoside drugs have shown antiviral activity. Two simple molecules with potent activity are phosphonoacetic... 

Zhang, J., Visser, F., King, K.M., Baldwin, S.A., Young, J.D. and Cass, C.E. (2007) The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. Cancer Metastasis Reviews, 26 (1), 85-110. 

Presently, the role of nucleoside transporters on the pharmacokinetics of nucleoside drugs is poorly... 

Figure 8.17 Top Guanosine and the acyclic nucleoside drugs Zovirax (acyclovir), and Cytovene (ganciclovir). Bottom three urotensin-II receptor agonists. (Croston, G.E., et al. Discovery of the first nonpeptide agonist of the GPR14/Urotensin-II receptor 3-(4-Chlorophenyl)-3-(2-(dimethylammo)ethyl)isochroman-l-one (AC-7954). J. Med. Chem. 2002, 45, 495(M953.)...

In an investigation of a possible way of delivering nucleoside drugs across cell membranes, the glucosyl phospholipid (115) of thymidine was prepared. This was found to interact with large unilamellar vesicles so as to place the nucleotide derivative Inside the vesicles, suggesting transport across the lipid bilayer. i Similar mannose phosphate derivatives of AZT, ddT and FDU were... 

Herdewijn P. Stmctural requirements for antiviral activity in nucleosides. Drug Deliv Today. 1997 2 235-242. 

---