ITC研究达卡巴嗪与DNA反应动力学

利用等温滴定量热(ITC)、光谱、粘度测量等方法,研究了小牛胸腺DNA与抗癌药物达卡巴嗪的相互作用。结果表明:达卡巴嗪与DNA作用后,吸收光谱会出现增色、蓝移和粘度减小等现象。采用ITC法得到了结合常数以及结合位点数,发现达卡巴嗪与DNA以非经典嵌插式及表面作用两种方式结合。对于嵌插式,ΔH10,ΔS10,K1=5.63×10~4,结合位点数0.10;对于药物分子仅与DNA表面发生作用而并未嵌入到DNA分子的疏水部分的结合方式,ΔH_20,ΔS_20,K_2=1.00×10~3,结合位点数9.99。同时发现紫外法得到的结合常数是Ka=6.70×10~4,与ITC的嵌插式吻合。

Interaction Dynamics Between Dacarbazine and DNA

The interaction between calf thymus DNA and anti-cancer drug dacarbazine was investiga-ted using isothermal titration calorimetry( ITC) , spectroscopy, viscosity and other methods. The hy-perchromic effect and blue shift in the absorption spectra as well as viscosity decline are observed clearly after the interaction between dacarbazine and DNA. Furthermore, the binding constant and number of binding sites are also recorded by ITC, presenting that the interactions of the dacarbazine with DNA can be categorized for two modes: a non-classical intercalation type and surface binding effect. In former,△H1 <0, △S1 >0, K1 =5. 63 × 104 , the binding site is 0. 10. In latter, only surficial interaction during the combination of the drug molecule with DNA occurs, not embedding into the hydrophobic part of the DNA molecule, due to△H2 > 0 ,△S2 > 0, K2 =1. 00 × 103 , and the binding site of 9. 99. Meanwhile, UV method is also employed to find the binding constant of Ka=6. 70 × 104 , which is consistence with ITC observation.