The Influence of the 2′OH Group upon the Binding of Nucleotides by Basic Polyamino Acids

Abstract

The position of the phosphate group on the ribose of nucleoside monophosphates markedly influences their binding behavior with basic polyamino acids, such as poly-L-lysine and poly-1;-arginine. Equilibrium dialysis of adenine and guanine derivatives has revealed that the binding of 5'-and 3'-ribonucleotides (group I, possessing a free 2'OH group) to basic polyamino acids is clearly different from that of 2'-rib0 and 5'-deoxyribonucleotides (group 11, the 2'OH group is blocked and absent, respect.). At low nucleotide to poly-L-lysine ratios, where the binding corresponds to the Langmuir isotherm, the binding constants of group I are smaller than those of group 11. At higher nucleotide to polypeptide ratios the binding is cooperative and accompanied by a phase transition : guanine derivatives of group I show precipitation with poly-L-lysine a t O", whereas with group I1 a gel-like phase is separated; with poly-L-arginine only precipitation occurs. Analysis of the cooperative binding with guanine nucleotides and poly-L-arginine revealed that group I possesses considerably higher nearest neighbour interaction energies than group 11.The stacking coefficients decrease in the order 3'-GMP > 5'-GMP > 5'-dGMP 7 2'-GMP. The implications of these results are discussed.

Drug‐Biomolecule Interactions: Interactions of Mononucleotides and Polybasic Amino Acids

“…These results, together with those already mentioned, make it clear that the association of the nucleotides with the basic polyamino acids consists of a primary electrostatic attraction, without which the interaction does not take place, and a secondary one, the or 5 X The cooperative nature of these interactions at high nucleotide concentrations has been treated in detail (14,18).…”

“…Several studies (18,19) examined the importance of the 2'-OH group. Circular dichroic spectra showed that guanosine 5'-monophosphate and guanosine 3'-monophosphate (with 2'-OH groups) both caused changes in the spectra of poly-L-lysine a t short wavelengths, indicating polyamino acid conformational change, and at high wavelengths, indicating association of the bases.…”

“…The cooperative nature of these interactions at high nucleotide concentrations has been treated in detail (14,18).…”

“…In model-building experiments (12), the 2'-OH groups of the nucleotides may have participated in nucleotide-nucleotide interactions through hydrogen bonding of the ribose on one nucleotide to the phosphoryl oxygen on a neighboring nucleotide. Several studies (18,19) examined the importance of the 2'-OH group. Circular dichroic spectra showed that guanosine 5'-monophosphate and guanosine 3'-monophosphate (with 2'-OH groups) both caused changes in the spectra of poly-L-lysine a t short wavelengths, indicating polyamino acid conformational change, and at high wavelengths, indicating association of the bases.…”