Biophysical Studies on the Effect of the 13 Position Substitution of the Anticancer Alkaloid Berberine on Its DNA Binding
Biophysical Studies on the Effect of the 13 Position Substitution of the Anticancer Alkaloid Berberine on Its DNA Binding
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DOI：
10.1021/jp210072a
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发表时间：
2012-02-23
影响因子：
3.3
通讯作者：
Kumar, Gopinatha Suresh
中科院分区：
文献类型：
--
作者：
Bhowmik, Debipreeta;Hossain, Maidul;Kumar, Gopinatha Suresh
研究了6种不同长度烷基链和C-13位末端苯基的小檗碱类似物与DNA结合的结构效应和热力学。所有的类似物结合DNA非合作相反，小檗碱的合作结合。结合亲和力较高，链长的影响仅达到（CH 2）（3），之后结合亲和力略有下降。嵌入结合与强稳定的DNA螺旋被揭示。结合导致碱基堆积减弱，B-型内的构象发生中度变化。在每种情况下，结合都是熵驱动的，熵对自由能的贡献随着链长的增加而增加，直到阈值（CH 2）（3）。在每种情况下，络合主要由非聚合电解力;聚合电解力在50 mM [Na +]下仅占总自由能的四分之一。总体而言，C-13位的苯基烷基取代显著增强了DNA结合，并且对于具有（CH2）的类似物最高（3）。的DNA结合方面的取代小檗碱的结构和热力学数据与小檗碱相比。
The structural effects and thermodynamics of the DNA binding of six berberine analogues with alkyl chains of varying length and a terminal phenyl group at the C-13 position were investigated. All the analogues bound DNA noncooperatively in contrast to the cooperative binding of berberine. The binding affinity was higher and the effect of the chain length was only up to (CH2)(3), after which the binding affinity decreased slightly. Intercalative binding with strong stabilization of the DNA helix was revealed. Binding resulted in the weakening of the base stacking with moderate conformational changes within the B-form. The binding was entropy driven in each case, the entropy contribution to the free energy increasing with the chain length up to the threshold (CH2)(3). The complexation was dominated by nonpolyelectrolytic forces in each case; polyelectrolytic forces contributed only a quarter to the total free energy at 50 mM [Na+]. Overall, the phenylalkyl substitution at the C-13 position considerably enhanced the DNA binding and was highest for the analogue with (CH2)(3). Structural and thermodynamic data on the DNA binding aspects of the substituted berberines are presented in comparison with berberine.