Synthesis of 5-(1-propynyl)-2’-deoxy-Uridine (pdU) and 5-(1-propynyl)-2’- deoxyCytidine (pdC) monomers for oligonucleotide synthesis demonstrated that both substitutions enhanced duplex stability while triplex binding was improved by substitution of pdU but destabilized by pdC. Substitution of methyl with 1-propyne at the C5 position of pyrimidines allowed better stacking of the bases since the propyne group is planar with respect to the heterocyclic base. At the same time, propyne is more hydrophobic than methyl and this property contributed to a further increase in binding.
The improved lipophilicity of the propyne group may also improve transport through cell walls. Duplex binding enhancement due to these modified bases was substantial (1.7 °C per pdU residue and 1.5 °C per pdC residue).