Efficient triple helix formation by oligodeoxyribonucleotides containing α- or β-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues

Abstract

Triple helices containing C+.G.C triplets are destabilised at physiological pH due to the requirement for base protonation of 2'-deoxycytidine (dC), which has a pK(a) of 4.3. The C nucleoside 2-amino-5-(2'-deoxy-β-D-ribofuranosyl)pyridine (β-AP) is structurally analogous to dC but is considerably more basic, with a pK(a) of 5.93. We have synthesised 5'-psoralen linked oligodeoxyribonucleotides (ODNs) containing thymidine (dT) and either β-AP or its α-anomer (α-AP) and have assessed their ability to form triplexes with a double-stranded target derived from standard deoxynucleotides (i.e. β-anomers). Third strand ODNs derived from dT and β-AP were found to have considerably higher binding affi..