Bhadra Kakali, Kumar Gopinatha Suresh
Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, Jadavour, Kolkata, India.
Biochim Biophys Acta. 2011 Apr;1810(4):485-96. doi: 10.1016/j.bbagen.2011.01.011. Epub 2011 Jan 31.
Interaction of isoquinoline alkaloids berberine, palmatine, coralyne and sanguinarine with human telomeric quadruplex DNA, dAGGG(TTAGGG)(3), has been investigated and compared with ethidium.
Biophysical techniques such as absorption, fluorescence, circular dichroism, optical melting and microcalorimetry have been used.
Absorption and fluorescence studies revealed noncooperative 1:1 binding for all the molecules. Coralyne showed highest affinity (10(6) M(-1)) and for others it was ~10(5) M(-1). The binding affinity varied as coralyne>sanguinarine>berberine>palmatine. Ethidium showed affinity close to sanguinarine. Comparative fluorescence quenching and polarization anisotropy of the emission spectra gave evidence for a stronger stacking interaction of coralyne and sanguinarine compared to berberine and palmatine. Circular dichroic spectral perturbations were similar in all the cases, but a strong induced circular dichroism for the bound molecules was observed only for coralyne and sanguinarine. The interaction of all the alkaloids was exothermic. Binding of coralyne and sanguinarine was predominantly enthalpy driven while that of berberine and palmatine was entropy driven. Heat capacity values of -169, -198, -105 and -95cal/molK, respectively, for coralyne, sanguinarine, berberine, and palmatine suggested significant differences in the hydrophobic contribution to the binding.
This study presents a complete structural and thermodynamic profile of the binding of isoquinoline alkaloids with G-quadruplex.
These results suggest strong and specific binding of these molecules to the G-quadruplex and highlight the differences in their structure in the interaction profile.
已对异喹啉生物碱小檗碱、巴马汀、珊瑚菜碱和血根碱与人端粒四链体DNA（dAGGG(TTAGGG)(3)）的相互作用进行了研究，并与溴化乙锭作比较。
采用了吸收光谱、荧光光谱、圆二色光谱、光学熔解曲线和微量量热法等生物物理技术。
吸收光谱和荧光光谱研究表明，所有分子均以非协同方式进行1:1结合。珊瑚菜碱表现出最高亲和力（10(6) M(-1)），其他分子的亲和力约为10(5) M(-1)。结合亲和力的变化顺序为：珊瑚菜碱>血根碱>小檗碱>巴马汀。溴化乙锭的亲和力与血根碱相近。发射光谱的比较荧光猝灭和偏振各向异性表明，与小檗碱和巴马汀相比，珊瑚菜碱和血根碱具有更强的堆积相互作用。所有情况下圆二色光谱扰动相似，但仅在珊瑚菜碱和血根碱中观察到结合分子的强诱导圆二色性。所有生物碱的相互作用均为放热反应。珊瑚菜碱和血根碱的结合主要由焓驱动，而小檗碱和巴马汀的结合则由熵驱动。珊瑚菜碱、血根碱、小檗碱和巴马汀的热容值分别为-169、-198、-105和-95cal/molK，这表明疏水作用对结合的贡献存在显著差异。
本研究给出了异喹啉生物碱与G-四链体结合的完整结构和热力学概况。
这些结果表明这些分子与G-四链体有强特异性结合，并突出了它们在相互作用模式上的结构差异。
