Charged oligopeptide-nucleic acid interactions as models of the electrostatic component of protein-nucleic acid interactions.

摘要

For oligolysines and oligoarginines containing one or more tryptophans, of net charge, z = +2 to +10, binding to various single-stranded (ss) and double-stranded (ds) nucleic acids, there is a linear relationship between logK{dollar}sb{lcub}rm obs{rcub}{dollar} and log(K{dollar}sp+{dollar}) (within the range of (K+) examined) up to 0.5 M (K{dollar}sp+{dollar}). The value of logK{dollar}sb{lcub}rm obs{rcub}{dollar} extrapolated to 1M K{dollar}sp+{dollar} was found to be approximately zero for each oligolysine-nucleic acid interaction {dollar}rm (Delta Gspcircsim0{dollar} kcal/mol for lysine-phosphate interactions), consistent with expectations for a ligand binding solely by electrostatic interactions. Of all salt types examined, fluoride and acetate produce systematically the highest K{dollar}sb{lcub}rm obs{rcub}{dollar} and lowest {dollar}rm vert(partial log Ksb{lcub}obs{rcub}/partial loglbrack Ksp+rbrack)vert,{dollar} indicating that these anions interact least-well with oligolysines and oligoarginines.; Upon binding an oligolysine or oligoarginine to polynucleotides, less than one monovalent cation is released thermodynamically per net oligopeptide charge. This fraction is 0.72({dollar}pm{dollar}0.04) for poly(U) and 0.91({dollar}pm{dollar}0.07) for ds-DNA, independent of peptide charge. Less than one cation is also released thermodynamically from poly(A), poly(C) and poly(dT) per peptide charge; however, this fraction is lower for peptides of higher charge (z {dollar}>{dollar} +4) binding to these polynucleotides.; The dependence of {dollar}rm Delta Gspcircsb{lcub}obs{rcub}{dollar} (K{dollar}sb{lcub}rm obs{rcub}){dollar} on monovalent salt-concentration for the binding of positively charged oligopeptides to each polynucleotide examined is due to entropic effects, likely resulting from cation release from the nucleic acid. {dollar}rm Delta Gspcircsb{lcub}obs{rcub}{dollar} and {dollar}rm Delta Hspcircsb{lcub}obs{rcub}{dollar} are more favorable for the arginine containing peptides, relative to lysine containing peptides, at constant (K{dollar}sp+{dollar}) {dollar}(Delta{lcub}rm G{rcub}spcirc{dollar} = {dollar}-{dollar}0.20({dollar}pm{dollar}0.13) kcal/mole arginine and {dollar}rm Delta Hspcircsb{lcub}obs{rcub}{dollar} = ({dollar}-{dollar}0.83({dollar}pm{dollar}0.54) kcal/mole arginine), independent of polynucleotide type. This behavior is consistent with hydrogen-bonding of the arginine to the phosphates of the nucleic acids.; The intrinsic free energy of binding of tryptophan to different ss-homopolynucleotides becomes less favorable in the order: poly(dT) {dollar}>{dollar} poly(U) {dollar}sim{dollar} poly(A) {dollar}gg{dollar} poly(C). For each polynucleotide examined, the value of {dollar}rm Delta Gspcircsb{lcub}Trp{rcub}{dollar} is independent of z due to a compensation of the favorable enthalpy of binding by unfavorable entropic contributions to the net free energy.