STEROID DIAMINE-NUCLEIC ACID INTERACTIONS - PARTIAL INSERTION OF DIPYRANDIUM BETWEEN UNSTACKED BASE-PAIRS OF THE POLY(DA-DT) DUPLEX IN SOLUTION

被引:43
作者
PATEL, DJ
CANUEL, LL
机构
关键词
D O I
10.1073/pnas.76.1.24
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The authors 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) 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 ω,ω'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.
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页码:24 / 28
页数:5
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