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Study of alkaloid berberine and its interaction with the human telomeric i-motif DNA structure
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy ( IF 4.4 ) Pub Date : 2020-11-13 , DOI: 10.1016/j.saa.2020.119185
R. Gargallo , A. Aviñó , R. Eritja , P. Jarosova , S. Mazzini , L. Scaglioni , P. Taborsky

The alkaloid berberine presents many biological activities related to its potential to bind DNA structures, such as duplex or G-quadruplex. Recently, it has been proposed that berberine may interact with i-motif structures formed from the folding of cytosine-rich sequences. In the present work, the interaction of this alkaloid with the i-motif formed by the human telomere cytosine-rich sequence, as well as with several positive and negative controls, has been studied. Molecular fluorescence and circular dichroism spectroscopies, as well as nuclear magnetic resonance spectrometry and competitive dialysis, have been used with this purpose. The results shown here reveal that the interaction of berberine with this i-motif is weak, mostly electrostatics in nature and takes place with bases not involved in C·C+ base pairs. Moreover, this ligand is not selective for i-motif structures, as binds equally to both, folded structure, and unfolded strand, without producing any stabilization of the i-motif. As a conclusion, the development of analytical methods based on the interaction of fluorescent ligands, such as berberine, with i-motif structures should consider the thermodynamic aspects related with the interaction, as well as the selectivity of the proposed ligands with different DNA structures, including unfolded strands.



中文翻译:

生物碱小ber碱及其与人端粒i-基序DNA结构相互作用的研究

生物碱小ber碱具有许多与其结合DNA结构的潜能有关的生物学活性,例如双链体或G-四链体。最近,有人提出小碱可以与富含胞嘧啶的序列折叠形成的i-基序结构相互作用。在目前的工作中,已经研究了该生物碱与人端粒富含胞嘧啶的序列形成的i-基序以及几种阳性和阴性对照的相互作用。为此,已经使用了分子荧光和圆二色性光谱学,以及核磁共振光谱法和竞争性透析法。此处显示的结果表明,小ber碱与该i-基序的相互作用较弱,本质上主要是静电,并且发生在不涉及C·C +的碱基的情况下碱基对。此外,该配体对i-基序结构没有选择性,因为它与折叠结构和未折叠链均等结合,而不会产生i-基序的任何稳定性。总之,基于荧光配体(例如小ber碱)与i-基序结构相互作用的分析方法的开发应考虑与相互作用相关的热力学方面,以及所提议的具有不同DNA结构的配体的选择性,包括展开的线。

更新日期:2020-11-13
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