Quantum Optics and Photon Physics, National Physical Laboratory, Dr. K.S. Krishnan Road, New Delhi 110 012, India.
J Photochem Photobiol B. 2011 Nov 3;105(2):143-8. doi: 10.1016/j.jphotobiol.2011.08.003. Epub 2011 Aug 18.
5-Fluorouracil (5FU) is an anticancer chemotherapeutic drug which exerts cytotoxic effect by inhibiting cellular DNA replication. In the present study, we explore the binding of 5FU with DNA and resulting structural and conformational changes on DNA duplex. UV-visible, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopic techniques were employed to explore these interactions. A constant concentration of calf thymus DNA was incubated with varying concentrations of 5FU. UV-visible and FTIR spectroscopic results revealed that intercalation is the primary mode of interaction between 5FU and nitrogenous bases of the nucleic acid. The binding constant was found to be 9.7×10(4); which is indicative of moderate type of interaction between 5FU and DNA duplex. It was also observed that 5FU intercalates slightly more between AT base pairs compared to GC pairs. FTIR and circular dichroism spectroscopic results revealed that 5FU disturbs native B-conformation of DNA though, DNA remains in its B conformation even at higher concentrations of 5FU.
5-氟尿嘧啶(5FU)是一种抗癌化疗药物,通过抑制细胞 DNA 复制发挥细胞毒性作用。在本研究中,我们探讨了 5FU 与 DNA 的结合以及对 DNA 双链体的结构和构象变化。采用紫外可见分光光度法、傅里叶变换红外(FTIR)和圆二色(CD)光谱技术来研究这些相互作用。在恒定浓度的小牛胸腺 DNA 中,用不同浓度的 5FU 孵育。紫外可见和 FTIR 光谱结果表明,5FU 与核酸的含氮碱基之间的主要相互作用方式是嵌入。结合常数为 9.7×10(4),表明 5FU 与 DNA 双链体之间存在中等强度的相互作用。还观察到 5FU 在 AT 碱基对之间的嵌入程度略高于 GC 对。FTIR 和 CD 光谱结果表明,尽管 5FU 会扰乱 DNA 的天然 B 构象,但即使在 5FU 的较高浓度下,DNA 仍保持其 B 构象。