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

The ability of BPAC(8), a member of the bis-pyridinium aldehyde (BPA) famil y with a linear octamethylene chain linking the two charged pyridinium moie ties, to covalently bond with a guanine residue at a 5'-CpG-3' site is stud ied. Three oligomers including a central CpG step with different conformati ons are studied. By H-1 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 t here 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 o f the oligomer. When the CpG structure is stiffened by a rigid nucleotide e nvironment, such as A-T tracts, the reaction with BPA is inhibited.