Open AccessSteroid diamine-nucleic acid interactions: partial insertion of dipyrandium between unstacked base pairs of the poly(dA-dT) duplex in solution.
Author(s) -
Dinshaw J. Patel,
Lita L. Canuel
Publication year - 1979
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.76.1.24
Subject(s) - diamine , chemistry , chemical shift , nucleic acid , steroid , stereochemistry , dna , base pair , polynucleotide , solvent , aqueous solution , nucleobase , organic chemistry , biochemistry , hormone
We report on an NMR investigation of steroid diamine.nucleic acid complexes as a function of phosphate-to-drug ratios in aqueous solution in order to evaluate the structural and kinetic aspects of the binding of a nonintercalative drug to a synthetic DNA in solution. The nonexchangeable proton chemical shift parameters for the dipyrandium.poly(dA-dT) complex demonstrate unstacking of base pairs and partial insertion of the steroid diamine at the complexation site. The chemical shifts and linewidths of the exchangeable protons as a function of pH demonstrate that the base pairs are intact but partially exposed to solvent at the steroid diamine binding site. The phosphorus chemical shifts suggest that the base pairs unstack upon complex formation without changes in the omega,omega' polynucleotide backbone torsion angles. The NMR line shape parameters require rapid exchange of the steroid diamine among potential binding sites and are consistent with greater segmental flexibility in the complex compared to the synthetic DNA in solution. The NMR experiments are discussed in relation to Sobell's proposed model [Sobell, H.M., Tsai, C.C., Gilbert, S.G., Jain, S.C. & Sakore, T.D. (1976) Proc. Natl. Acad. Sci USA 73, 3068-3072] for the steroid diamine-DNA complex.