Spectroscopic and calorimetric studies on the binding of the phototoxic and cytotoxic plant alkaloid sanguinarine with double helical poly(A)

Spectroscopic and calorimetric studies on the binding of the phototoxic and cytotoxic plant alkaloid sanguinarine with double helical poly(A)
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DOI:
10.1016/j.jphotochem.2007.07.022
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发表时间:
2008-02-20
影响因子:
4.3
通讯作者:
Kumar, Gopinatha Suresh
Kumar, Gopinatha Suresh
中科院分区:
化学3区
文献类型:
--
作者:
Giri, Prabal;Kumar, Gopinatha Suresh

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利用多方面的光谱和量热技术研究了具有光毒性和细胞毒性的DNA结合植物生物碱血根碱与双链聚腺苷酸的相互作用。血根碱的吸收光谱的减色和红移以及荧光强度的大幅增强表明生物碱与双链聚(A)的强结合。相应的内在结合常数的络合,从可见光吸收和荧光光谱法,分别获得,被认为是在10(4)M-1的顺序。结合的进一步特征在于从腺嘌呤碱基对到生物碱的强能量转移,生物碱的荧光的显著偏振,对双链体的热链分离的稳定,并且还导致聚(A)中的显著构象变化,伴随着在结合的生物碱分子中的光学活性的产生,否则是非手性的。等温滴定量热法和差示扫描量热法的研究表明,结合的生物碱是放热和焓驱动。所有这些结果与荧光猝灭实验一起为生物碱血根碱插入到双链聚(A)中提供了良好的证据。(C)2007 Elsevier B. V.保留所有权利。
The interaction of the phototoxic and cytotoxic DNA binding plant alkaloid sanguinarine with double stranded polyadenylic acid has been investigated from multifaceted spectroscopic and calorimetric techniques. The hypochromic and bathochromic shifts in the absorption spectrum, and large enhancement of the fluorescence intensity of sanguinarine indicated strong binding of the alkaloid to the duplex poly(A). The corresponding intrinsic binding constant for the complexation, obtained from visible absorbance and fluorescence spectroscopic methods, respectively, was found to be in the order of 10(4) M-1. The binding was further characterized by strong energy transfer from the adenine base pairs to the alkaloid, significant polarization of the fluorescence of the alkaloid, stabilization against thermal strand separation of the duplex, and also resulting in remarkable conformational changes in poly(A) with concomitant generation of optical activity in the bound alkaloid molecules that are otherwise achiral. Isothermal titration calorimetric and differential scanning calorimetric studies revealed the binding of the alkaloid to be exothermic and enthalpy driven. All these results together with fluorescence quenching experiments advance good evidence for the intercalation of the alkaloid sanguinarine into the duplex poly(A). (C) 2007 Elsevier B.V. All rights reserved.