Covalent bonding of bridged pyridinium aldehyde derivatives with guanine N7 is controlled by CpG site conformation

Abstract

The ability of BPAC₈, a member of the bis-pyridinium aldehyde (BPA) family with a linear octamethylene chain linking the two charged pyridinium moieties, to covalently bond with a guanine residue at a 5′-CpG-3′ site is studied. Three oligomers including a central CpG step with different conformations are studied. By ¹H NMR spectroscopy and gel analysis it is established that the covalent reaction occurs for the decamer CRE, d(ATGACGTCAT), and to a lesser extent for the methylated dodecamer, d(GAAAAmeCGTTTTC), while there is no reaction for the sequence d(GAAAACGTTTTC). The ease of reaction with BPA is correlated with both the geometry of CpG and the malleability of the oligomer. When the CpG structure is stiffened by a rigid nucleotide environment, such as A–T tracts, the reaction with BPA is inhibited.