Cation-Dependence of the Self-Association Behavior of Guanylyl-(3′-5′)-Guanosine

Abstract

The aggregation behavior of guanylyl-(3′-5′)-guanosine, GpG, in the form of the tetramethylammonium (TMA), Li, Na, and K salts in aqueous solution has been investigated by NMR and FTIR techniques. The salts were prepared by a cation-exchange method. The ability of the cations to induce aggregate formation is TMA⁺ < Li⁺ < Na⁺ < K⁺, where TMA⁺ has only a weakly promoting action and K⁺ has a very strong effect. Three types of aggregates have been observed: (a) small aggregates which are in rapid exchange with respect to the NMR time scale; (b) intermediate-sized aggregates which are slow to exchange; (c) very large aggregates which can only be observed by FTIR. In all cases the aggregated species are held together by base stacking and guanine-guanine hydrogen bonding. A stoichiometry of 2 GpG per K⁺ has been determined by a ¹H NMR titration of TMAGpG with KCl. Models have been proposed for the various-sized species. These include stacked dimers, stacked tetramers (similar to G- tetrads), and species in which K⁺ ion bridges between phosphates in separate tetramers.