The effect of monovalent cations on the self-association of cytidylyl-(3-5')-guanosine and guanylyl-(3'5')-cytidine in aqueous solution.

ABSTRACT

The hydrogen-bonding, base stacking, and formation of extended aggregates has been investigated for salts of guanylyl-3'-5')-cytidine, GpC, and cytidylyl-(3'-5')- guanosine, CpG, in which the cation was Na+, K+, or tetramethylammonium (TMA+). Variable temperature studies were done at 2-70 degrees C on aqueous solutions at pD4 and 8 using 1H NMR and FTIR. At low temperatures it has been found that at pD 8 both GpC and CpG form Watson-Crick dimers which stack upon each other to form larger species. A slight cation effect is observed below 35 degrees C which has the order TMA+ > Na+ > K+. This order suggests that the cations are interacting with the phosphate and interactions with the bases are unlikely. The 1H NMR spectrum for TMACpG at pD 4 has been assigned and exhibits chemical shift differences from those at pD 8 which are consistent with protonation of the N3 of the cytidine residue. Based on NMR line broadening, CpG at pD 4 has a greater degree of self-association at low temperature than it or GpC have at pD 8. A different type of hydrogen bonding and self-association occur in CpG at pD 4 compared to pD 8, but the structures are uncertain. Due to hemi-protonation of the cytidine N3, parallel G-G/C-C+ base paired dimers or G-tetrads may be forming.