Dept. of Chemical Engineering and Analytical Chemistry, University of Barcelona, Marti i Franquès 1, E-08028 Barcelona, Spain.
Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), CIBER-BBN, Jordi Girona 18-26, E-08034 Barcelona, Spain.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 5;248:119185. doi: 10.1016/j.saa.2020.119185. Epub 2020 Nov 13.
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.
生物碱小檗碱具有许多与结合 DNA 结构相关的生物活性，例如双链体或 G-四联体。最近，有人提出小檗碱可能与由富含胞嘧啶序列折叠形成的 i- 型结构相互作用。在本工作中，研究了该生物碱与人端粒富含胞嘧啶序列形成的 i- 型结构以及几个阳性和阴性对照之间的相互作用。为此目的，使用了分子荧光和圆二色性光谱以及核磁共振谱和竞争透析。这里显示的结果表明，小檗碱与该 i- 型结构的相互作用较弱，主要是静电性质，并且发生在不参与 C·C 碱基对的碱基上。此外，该配体对 i- 型结构没有选择性，因为它与折叠结构和未折叠链同等结合，而不会使 i- 型结构产生任何稳定化。总之，基于荧光配体（如小檗碱）与 i- 型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，以及与不同 DNA 结构（包括未折叠链）的配体的选择性。
