Model considerations on physico-chemical nature of protein-nucleic acid contacts through amino acid carboxylic groups: spectroscopic data

This paper generalizes the results of a series of the works on spectroscopic (IR, UV, NMR, Raman) investigations of complexes of nucleotide bases, their numerous methyl and glycosyl derivatives with amino acid carboxylic groups modelling point protein-nucleic acid contacts. The specificity of interactions between bases and two forms of carboxylic group — neutral and deprotonated — was determined. The structures of the complexes investigated were established, and the role of various atomic groups in their formation was elucidated as well. Special consideration has been given to the frequent occurrence of proton transfer in the studied complexes. The significance of the data obtained in understanding of elementary mechanisms of protein-nucleic acid interactions is discussed.

Among non-substituted nucleotide bases and nuc leosides only Cyt, weakly interacting with depro tonated carboxylic group (carboxylate-ion), was sho wn to form the strong complex with neutral carboxylic group through two H-bonds involving N3 atom and amino group or N1H and C=0 groups (according to the AMI calculations [32] the latter scheme is prevailing) (Fig. 1). The results of IR and Raman investigations of solid state complexes of cytosine and amino acid carboxylic groups [23, 28 ], as well as ,3 C NMR study in DMSO [25] evidence the proton transfer from carboxylic group to the base along the OH..,N3 bond. Moreover, it was shown that in the triple complex f-Asp:Cyt:m 9 Gua amino acid carboxylic group, binding to Cyt, loosens H-bonds inside the base pair.
Quite the contrary, the other bases and nuc leosides form specific complexes with carboxylate-ion, their interactions with neutral carboxylic group were not observed. Nevertheless, such interactions may be realized in less polar environment [33] in which the solvatation of the ligands is lower.
It was demonstrated that imino and amino groups of the bases have a dominant role in formation of their complexes with carboxylate-ion. The monomethylation of Gua and Ade amino groups doesn't SAMIJLBNKO S P. ВТ AL change the character of interaction with carboxylateion, increasing it considerably. To the point, the significant role of inversion and anisotropic rotation of the nucleotide bases' amino groups in DNA structure and fuctioning is discussed in the papers [34-38 ].  dimethylcytosine (a, b), cytidine, deoxycytidine, 5-methyldeoxycytidine (c) with neutral carboxylic group; cytosine, 5-methylcytosine (d) y cytidine, deoxycytidine, 5-methyl deoxycytidine (e) with carboxylate-ion. Hereinafter abbreviations are R e H, CH^; rib(drib) -ribose(deoxyribose) Carboxylate-ion forms highly specific complex with m 9 Gua and G through two H-bonds involving the N1H imino and N2H amino groups, Ade -N6H amino and N7H imino groups [39 ] (the N9H -» N7H tautomeric transition of Ade complexed with car boxylate-ion was borne out by the quantum-chemical calculations [32]), Hyp -N1H and/or N9H imino groups, I -N1H imino group, X and m 9 Xan -N3H imino groups, Xan -N3H and N9H imino groups, m 3 Xan -N9H imino group (the N7H N9H tau tomeric transition of Xan and m 3 Xan complexed with carboxylate-ion was confirmed by quantum-chemical simulations [32]), Ura and Thy -N1H and/or N3H imino groups, U and T -N3H imino groups (Fig. 2) The obtained set of physico-chemical features of point protein-nucleic acid contacts is consistent with X-ray and NMR data concerning detailed architecture of nucleic acids complexes with various enzymes, regulatory proteins and drugs of peptidic nature and Up-to-date physico-chemical biology attaches a great importance to proton transfer processes [52][53][54], which determine dynamic aspects of interactions between biopolymers, especially in nucleoproteid com plexes.
It might be worth pointing that proton transfer processes determined by two well structure of the H-bond potentials are substantially nonlinear and environmental dependent. The proton polarizability of such H-bonds (ability of shifting along the H-bonds) may exceed electron polarizability by two orders [55 ] and increases while chains of H-bonds are formed because of collective motion of protons [56 ]. There is an idea, that chains of H-bonds with such potentials in real biopolymers and their complexes may be one of the causative factors of their non-linear dynamics and the possible routes for the signals of long-range control of biochemical reactions. It is the complexes investigated that give an impetus to conformational transitions and biochemical transformations at long distances.
Much part of the work was sponsored by the ISF (grant K1F100).  Lamerichs R. M. /. N., Boelens R., Marel G. К et al