Abstract：The interaction of DNR-D3(daunorubicin derivative)synthesized in our laboratory with ctDNA was investigated by UV spectrum and fluorescence spectrum under physiological conditions (pH 7.4) for the first time. The red shifts and hypochromicities were observed from the absorption titration experiments. These results suggest that DNR-D3 was intercalated into the DNA base pairs. Through the fluorescence quenching data measured at different temperatures (20 ℃, 30 ℃ and 37 ℃), it is known that the quenching mechanism of fluorescence of DNR-D3 by ctDNA is a static quenching type. On the other hand, the binding constant, the number of binding sites and thermodynamic parameters were also obtained. These data also indicate that the binding mode of the interaction between DNR-D3 and ctDNA is intercalation. Additionally, the types of interaction force are mainly hydrogen bonding and electrostatic interaction, and the binding is exothermic enthalpy-entropy cooperative driven process. When the degree of fluorescence quenching of DNR-D3 is 50%, the ratio of the molar concentration of DNR-D3 to ctDNA is 7/25, which indicates that the DNR-D3 anthracycline was intercalated into the DNA base pairs and that DNR-D3 showed a strong anticancer activity. DNR-D3 is expected to become one of the drug candidates from our investigations.
吕 娟，王公轲，张贵生，刘青锋，卢 雁*. 光谱法研究柔红霉素衍生物DNR-D3与DNA相互作用[J]. 光谱学与光谱分析, 2010, 30(05): 1324-1328.
Lü Juan, WANG Gong-ke, ZHANG Gui-sheng, LIU Qing-feng, LU Yan* . Study on the Interaction between DNR-D3(Daunorubicin Derivative)and ctDNA by Spectroscopic Methods . SPECTROSCOPY AND SPECTRAL ANALYSIS, 2010, 30(05): 1324-1328.
[1] Liu S C, Liu Y J, Li J. J. Biochem. Biophys. Methods, 2005, 63: 125. [2] Bischoff G, Hoffmann S. Curr. Med. Chem., 2002, 9: 321. [3] Zagotto G, Gatto B, Moro S, et al. J. Chromato. B, 2001, 764: 161. [4] Stefania M, Rosanna M, Enzio R. J. Chem. Soc., Perkin Trans., 1998, 2: 1983. [5] Minotti G, Licata S, Saponiero. Chem. Res. Toxicol., 2000, 13: 1336. [6] Jolles B, laigle A. Chemico-Biological Interaction, 1996, 100: 165. [7] Zhang G S, Fang L Y, Zhu L Z, et al. J. Med. Chem., 2005, 48: 5269. [8] Zhang G S, Fang L Y, Zhu L Z, et al. J. Med. Chem., 2006, 49: 1792. [9] Kapuscinski J, Darzynkiewicz Z. Biochem. Pharmacol., 1985, 34: 4203. [10] XU Yan-ying, LI Hua, CAO Shu-wen, et al(徐燕影，李 华，曹树稳，等). Spectroscopy and Spectral Analysis(光谱学与光谱分析)，2008, 28(7): 1587. [11] TANG Hong-wu, CHEN Pei, ZENG Yun-e, et al(唐宏武，陈 蓓，曾云鹗，等). Chemical Journal of Chinese Universities(高等化学学报), 1997, 18: 1960. [12] Kumar C V, Emma H A. J. Am. Chem. Soc., 1993, 115(19): 8547. [13] LIU Xue-feng, XIA Yong-mei, LIU ling-ling, et al(刘雪峰，夏咏梅，刘玲玲, 等). Acta Chimica Sinica(化学学报), 2004, 62: 1484. [14] YAN Cheng-nong, PAN Zu-ting, LIU Yi, et al(颜承农，潘祖亭，刘 义, 等). Chinese Journal of Analytical Chemistry(分析化学), 2004, 32: 317. [15] Ashoka S, Seetharamappa J, Kandagal P B, et al. J. Lumin., 2006, 121(1) : 179. [16] Klotz I M, Urquhart J M. J. Am. Chem. Soc, 1949, 71(3): 847. [17] Ross P D, Subramanian S. J. Biochemistry, 1981, 20(11): 3096. [18] Takenaka S, Ihara T, Takagi M. J. Chem. Soc. Chem. Commun., 1990, 21: 1485. [19] Wiong C. Inorg. Chim. Acta, 1986, 123: 221. [20] Li N, Ma Y, Yang C, et al . Biophysical Chemistry, 2005, 116: 199.
