DNA Binding of Tilorone: 1H NMR and Calorimetric Studies of the Intercalation Export

@article{citeulike:4163244, abstract = {doi: 10.1021/bi602402m The fluorene derivative tilorone has received great attention as a DNA intercalator and has been widely recognized as an inducer of interferon. The biological activity of tilorone is known to be related to its binding mode with DNA; however, few structural and thermodynamic studies have elaborated on this issue. This paper presents two-dimensional (2-D) NMR and isothermal titration calorimetry (ITC) for the tilorone/DNA complex, coupled with circular dichroism (CD) spectroscopy and viscosity measurements. NMR investigation suggests that tilorone binds to DNA through intercalation, showing greater affinity for insertion between AT base pairs than between CG pairs. CD spectral changes were observed for T/B (tilorone/DNA base pair molar ratio) ratios greater than the stoichiometric ratio generally expected for intercalators (i.e., T/B = 0.5, according to the neighbor-exclusion principle). However, there was a clear plateau in the CD intensity between T/B < 0.35 and T/B > 0.45. From comparison with NMR and other measurements, we postulate that CD changes below the plateau should be related to the intercalation and the latter to electrostatic interactions and nonspecific bindings. ITC data showed that DeltaH < TDeltaS < 0, which indicated that tilorone/DNA binding is enthalpy controlled. The magnitude of Kb (the binding constant) was of the same order as that of ethidium bromide. The stoichiometric number, obtained from ITC, CD, and UV data, implied a relatively smaller value (0.280.35) than that of the neighbor-exclusion principle. This is because side chains located in the groove disrupt further intercalation to the adjacent sites.}, author = {Nishimura, Tomoki and Okobira, Tadashi and Kelly, Andrew M. and Shimada, Naohiko and Takeda, Yoichi and Sakurai, Kazuo}, citeulike-article-id = {4163244}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi602402m}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi602402m}, day = {1}, doi = {10.1021/bi602402m}, journal = {Biochemistry}, keywords = {binding, calorimetric, dna, nmr}, month = {July}, number = {27}, pages = {8156--8163}, posted-at = {2009-03-10 21:35:59}, priority = {2}, title = {DNA Binding of Tilorone: 1H NMR and Calorimetric Studies of the Intercalation}, url = {http://dx.doi.org/10.1021/bi602402m}, volume = {46}, year = {2007} }

TY - JOUR ID - citeulike:4163244 L3 - citeulike-article-id:4163244 N2 - doi: 10.1021/bi602402m The fluorene derivative tilorone has received great attention as a DNA intercalator and has been widely recognized as an inducer of interferon. The biological activity of tilorone is known to be related to its binding mode with DNA; however, few structural and thermodynamic studies have elaborated on this issue. This paper presents two-dimensional (2-D) NMR and isothermal titration calorimetry (ITC) for the tilorone/DNA complex, coupled with circular dichroism (CD) spectroscopy and viscosity measurements. NMR investigation suggests that tilorone binds to DNA through intercalation, showing greater affinity for insertion between AT base pairs than between CG pairs. CD spectral changes were observed for T/B (tilorone/DNA base pair molar ratio) ratios greater than the stoichiometric ratio generally expected for intercalators (i.e., T/B = 0.5, according to the neighbor-exclusion principle). However, there was a clear plateau in the CD intensity between T/B < 0.35 and T/B > 0.45. From comparison with NMR and other measurements, we postulate that CD changes below the plateau should be related to the intercalation and the latter to electrostatic interactions and nonspecific bindings. ITC data showed that DeltaH < TDeltaS < 0, which indicated that tilorone/DNA binding is enthalpy controlled. The magnitude of Kb (the binding constant) was of the same order as that of ethidium bromide. The stoichiometric number, obtained from ITC, CD, and UV data, implied a relatively smaller value (0.280.35) than that of the neighbor-exclusion principle. This is because side chains located in the groove disrupt further intercalation to the adjacent sites. IS - 27 JF - Biochemistry EP - 8163 TI - DNA Binding of Tilorone: 1H NMR and Calorimetric Studies of the Intercalation VL - 46 SP - 8156 KW - binding KW - calorimetric KW - dna KW - nmr AU - Nishimura, Tomoki AU - Okobira, Tadashi AU - Kelly, Andrew AU - Shimada, Naohiko AU - Takeda, Yoichi AU - Sakurai, Kazuo PY - 2007/07/01/ UR - http://dx.doi.org/10.1021/bi602402m ER -