Controlling the transmembrane transport of nucleosides

2014-05-19T14:54:19Z (GMT) by Gretchen Marie Peters Jeffery T. Davis
<div><p>Nucleoside analogues are used as drugs. Due to their hydrophilicity, nucleosides are poorly permeable to membranes and transporter proteins are required for efficient uptake. One approach towards improving membrane permeability of nucleosides is to use synthetic transporters. We describe ways to control transport of nucleosides across a liquid membrane. Hexanoylguanosine <b>1</b> selectively extracts and transports cytidines across a CHCl<sub>3</sub> membrane. Transport catalysed by G <b>1</b> was influenced by the nucleoside's sugar, with a selectivity of dC <b>4</b> > rC <b>3</b> > araC <b>5</b>. Selective transport could be modulated by adding compounds to the aqueous source phase or to the organic phase. Addition of K<sup>+</sup>2,6-DNP<sup>–</sup><b>8</b> to CHCl<sub>3</sub> containing G <b>1</b> switched off transport of rC <b>3</b> and dC <b>4</b> due to formation of a G-quartet assembly. A lipophilic G <b>1</b>·C <b>2</b> base pair could not transport dC <b>4</b>, but did catalyse transport of dG <b>7</b> across the CHCl<sub>3</sub> barrier. We propose that transport occurs because of formation of a base triple G <b>1</b>·C <b>2</b>·dG <b>7</b>. Addition of Na<sub>2</sub>B<sub>4</sub>O<sub>7</sub><b>9</b> to a source phase containing rC <b>3</b>, dC <b>4</b> and araC <b>5</b> shuts down transport of rC <b>3</b> by G <b>1</b>, due to formation of borate esters. These results indicate that one can control the selective transport of nucleosides.</p></div>