The interaction of nucleosides in aqueous solution

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Abstract

The interactions of nucleosides in aqueous solution were adopted as a model system for studying the nature of the balance of forces which maintains the structure of nucleic acids. The interactions were investigated using the experimental techniques of thermal osmometry, equilibrium ultracentrifugation, and ultraviolet spectroscopy. The data were analyzed with the aid of mathematical models for multiple association reactions.

For the nucleosides, deoxyadenosine, deoxyguanosine, inosine, purine riboside, deoxycytidine, deoxythymidine, and uridine, simple base pairing by means of hydrogen bonds was excluded. Complexes larger than dimers were indicated. Standard free energies for nucleoside association ranged from −1.5 kcal./mole for deoxyadenosine to +210 cal./mole for uridine. The interaction free energy was more negative for purine-purine than for pyrimidine-pyrimidine type interactions. These results suggest that, in aqueous solution, in the absence of co-operative macromolecular effects, the dominant forces of interaction between nucleosides result in the parallel stacking of their constituent bases. The hypochromism observed for deoxyadenosine is in accord with current theory which attributes hypochomicity to base stacking.

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    This research was partially supported by grants from the National Cancer Institute (CA 4216) and the National Science Foundation. One of us (T.N.S.) gratefully acknowledges a Pre-doctoral Fellowship from the United States Public Health Service awarded for part of this work.

    Present address: Department of Biochemistry, Colorado State University, Fort Collins, Colorado 80521, U.S.A.

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