Nucleoside transporter proteins: emerging targets for drug discovery

Abstract

Nucleosides are central salvage metabolites and, as precursors of nucleotides, play an essential role in intermediary metabolism and biosynthesis, as well as signal transduction through interaction with purinergic receptors. Nucleoside analogues are used to treat haematological malignancies, certain solid tumours and many viral diseases. Because most nucleosides are relatively hydrophilic molecules, the presence of specialised transporter proteins in plasma membranes is essential for cellular uptake. Nucleoside transport is mediated by either bi-directional equilibrative processes, driven by chemical gradients, or inwardly directed concentrative processes, driven by sodium gradients. Recent advances in the identification of nucleoside transporter proteins from humans and lower organisms, using molecular cloning and functional expression of cDNAs, have transformed our understanding of nucleoside transport processes. Most of the nucleoside transporters identified thus far are members of two previously unrec...