Abstract
The binding of quinolones, nalidixic acid (Nal), oxolinic acid (Oxo) with double stranded polynucleotides was undertaken by using UV-melting, UV-Vis absorption, fluorescence and CD spectroscopic techniques. The binding of Nal or Oxo to the polynucleotides under low- salt buffer conditions were determined for poly (dA)·(dT), poly [d(A-T)], poly (dG)·(dC), poly [d(G-C)] and E. coli DNA. The fluorescence data were analyzed using a previously established two step mechanism with two different DNA-Drug complexes [Rajeswari et al, Biochemistry 26, 6825–31 (1987)]. The first complex [DN]1 with a binding constant K1, is formed where the interactions are ‘nonspecific’ and complex [DN]2 with a binding constant K2, is formed where the interactions are “specific” which involve (additional) hydrophobic type of interactions like ‘stacking’ of the drug and the overall association constant is represented as K(=K1K2). The order of binding for Nal and Oxo is: poly [d(G-C)] > poly [d(A- T)] > E. coli > poly (dG)·(dC) > poly (dA)·(dT). Interaction of quinolones seems to be preferential in the alternating G, C or A, T stretches of DNA than those of non-alternating. Within any alternating or non-alternating in DNA sequences the G, C rich sequences have distinctly greater binding than A, T sequences. The overall association constant data (K) reveal higher binding of Oxo to DNA compared to Nal to any given polynucleotide investigated; which also explains the higher antibacterial potency of Oxo. Changes in the absorption difference spectra and in circular dichroic spectra also manifest these results. As the melting temperatures of the polynucleotides were only marginally raised in presence of the quinolone, we rule out the possibility of ‘classical intercalation’ of the drug. Amino group of guanine facilitates the binding of quinolones and therefore has the greater binding with the DNA. However, poly (dG)·(dC) is known to exist in ‘A’ conformation which is not adopted by quinolones as in the case of poly (dA)·(dT). Present results suggest that Nal or Oxo bind to DNA in a non-classical fashion which is partially stacking in nature.
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