Premium
On the interaction of daunomycin with synthetic alternating DNAs: Sequence specificity and polyelectrolyte effects on the intercalation equilibrium
Author(s) -
Xodo Luigi Emilio,
Manzini Giorgio,
Ruggiero João,
Quadrifoglio Franco
Publication year - 1988
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360271112
Subject(s) - chemistry , intercalation (chemistry) , polyelectrolyte , base pair , dna , binding site , crystallography , stereochemistry , quenching (fluorescence) , fluorescence , inorganic chemistry , polymer , organic chemistry , biochemistry , physics , quantum mechanics
The interaction of daunomycin with ctDNA and six purine–pyrimidine alternating poly‐deoxynucleotides has been studied using fluorometric and uv‐visible absorption methods. In the explored binding range of r > 0.05, the intercalation of the drug into the DNAs proved to be anticooperative, as indicated by the pronounced upward curvature of all the Scatchard plots obtained. The experimental data have been analyzed according to the recent theory of Friedman and Manning, which describes the polyelectrolyte effects on the site binding equilibria, drug intercalation included. We found that, accounting for the polyelectrolyte effects in the neighbor site exclusion model, the experimental data were nearly equally well described, in a wide range of binding ratios, by assuming the presence of sequence specificity effects (site size = 2 base pairs, exclusion parameter n = 1) or its absence (site size = 1 base pair, n = 1.7). The relevant results are as follows: (a) Daunomycin binds to all the DNAs considered with a stoichiometry of approximately 1 drug for every two base pairs. (b) The anticooperative nature of the interaction is essentially polyelectrolytic in origin. (c) The binding affinity shown by the drug for the different sites considered decreases in the order of Gm 5 C > AT > AC‐GT > IC > GC > AU, indicating a stabilizing effect of the —CH 3 group in position 5 of the pyrimidines. (d) The extent of quenching of the intrinsic fluorescence of daunomycin in the presence of DNA is bound to the presence, at the intercalation site, of a guanine residue, since GC, Gm 5 C, and AC‐GT sites induce a nearly total quenching, whereas AT, AU, and IC sites act only partially in this respect. The structural results obtained from the daunomycin‐d[(CGTACG)] 2 crystal suggest that the 2‐NH 2 group of guanine might be responsible for such a phenomenon. The influence of both the temperature and the ionic strength on the free energy of drug intercalation into ctDNA, poly[d(G‐C)] : poly[d(G‐C)], and poly[d(A‐C)] : poly[d(G‐T)] is examined and discussed.