Berberine-DNA complexation: New insights into the cooperative binding and energetic aspects

Berberine-DNA complexation: New insights into the cooperative binding and energetic aspects
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DOI:
10.1016/j.bbagen.2008.05.005
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发表时间:
2008-09-01
影响因子:
3
通讯作者:
Kumar, Gopinatha Suresh
Kumar, Gopinatha Suresh
中科院分区:
生物学3区
文献类型:
--
作者:
Bhadra, Kakali;Maiti, Motilal;Kumar, Gopinatha Suresh

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本文研究了具有细胞毒性的植物生物碱小檗碱与多种dna的平衡结合及其相互作用的能量学。当生物碱与碱基对的结合比例较低时,与At和GC序列比例几乎相等的天然dna的结合表现出协同性。相反,这种结合对以高AT OF GC序列为主的dna是不合作的。在合成的dna中,观察到与poly(dA)的协同结合。poly(dT)和poly(dG)。聚(dC)与聚(dA-dT)发生非协同结合。poly(dA-dT)和poly(dG-dC).poly(dG-dC)。合作和非合作结合均显著依赖于培养基的盐浓度。聚(dA)中In k与[Na+]的线性图。poly(dT)和poly(dA-dT)。聚(dA-dT)每结合生物碱分别释放0.56和0.75个钠离子。等温滴定量热法的结果显示,除了两种AT聚合物和富含AT的DNA外,所有DNA的结合都是放热的,并受到焓和熵变化的影响,在这两种DNA中,这种结合主要是熵驱动的。小檗碱与聚(dA)结合的热容值(δ Cp度)。保利(dT),聚(dA-dT)。聚(dA-dT)、产气荚膜梭菌和小牛胸腺DNA分别为-98、-140、-120和- 110 cal/mol K。这项研究为DNA构象中依赖碱基对异质性的结合提供了新的见解,并首次完整地描述了小檗碱与DNA结合的热力学特征。(c) 2008年Elsevier B.V.出版
The equilibrium binding of the cytotoxic plant alkaloid berberine to various DNAs and energetics of the interaction have been studied. At low ratios of bound alkaloid to base pair, the binding exhibited cooperativity to natural DNAs having almost equal Proportions of AT and GC sequences. In contrast, the binding was non-cooperative to DNAs with predominantly high AT OF GC sequences. Among the synthetic DNAs, cooperative binding was observed with poly(dA).poly(dT) and poly(dG).poly(dC) while noncooperative binding was seen with poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC). Both cooperative and non-cooperative bindings were remarkably dependent on the salt concentration of the media. Linear plots of In K. versus [Na+] for poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) showed the release of 0.56 and 0.75 sodium ions respectively per bound alkaloid. Isothermal titration calorimetry, results revealed the binding to be exothermic and favoured by both enthalpy and entropy changes in all DNAs except the two AT polymers and AT rich DNA, where the same was predominantly entropy driven. Heat capacity values (Delta Cp degrees) of berberine binding to poly(dA).poly(dT), poly(dA-dT).poly(dA-dT), Clostridium perfringens and calf thymus DNA were -98, -140, -120 and - 110 cal/mol K respectively. This study presents new insights into the binding dependent base pair heterogeneity in DNA conformation and the first complete thermodynamic profile of berberine binding to DNAs. (c) 2008 Published by Elsevier B.V.