Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364002, India.
Academy of Scientific and Innovative Research, CSIR-CSMCRI, Bhavnagar, Gujarat, 364002, India.
J Mol Model. 2020 Feb 1;26(2):38. doi: 10.1007/s00894-019-4282-2.
Small neutral seleno molecules were designed to stabilize G-quadruplex-DNA to accelerate the death of cancer cells. A new approach was considered in this study to design new ligands to stabilize G-quadruplex-DNA using the non-covalent σ-hole interaction. The systematic study has been performed with ligands in the absence and presence of σ-hole interaction to stabilize G-tetrad. Fluorine-substituted seleno ligands interact with the bases of G-quadruplex strongly with the σ-holes present in the ligands. The binding of the fluorinated ligands FSeCFSeCF SeF2(4) (75.0 kcal/mol) is stronger than that of BRACO-19 (70.0 kcal/mol) calculated at the same level of theory with G-tetrad. It is reported that BRACO-19 is employed to inhibit the enzymatic activity of telomerase. The calculated results also reveal the importance of optimum chain length of ligands to achieve a better binding ability with G-tetrad. The MESP calculations and AIM analysis corroborate the trends of binding of these ligand molecules with G-quadruplexes. The small neutral molecules possess considerable advantage to pass through the lipid bilayer of the cell membrane by passive transport and are of choice in biological research and for clinical trials. Graphical AbtractSmall neutral ligands with σ-holes can stabilize G-quadruplex to inhibit enzymatic activity of telomerase.
小分子中性硒化合物被设计用来稳定 G-四链体 DNA，以加速癌细胞的死亡。本研究考虑了一种新方法，即利用非共价 σ-hole 相互作用设计新的配体来稳定 G-四链体 DNA。这项系统研究是在没有和存在 σ-hole 相互作用的情况下进行的，目的是稳定 G-四联体。氟取代的硒配体与 G-四链体的碱基强烈相互作用，配体中存在 σ 空穴。与在相同理论水平下计算的 BRACO-19（70.0 kcal/mol）相比，氟化配体 FSeCFSeCF SeF2(4)（75.0 kcal/mol）与 G-四联体的结合更强。据报道，BRACO-19 被用于抑制端粒酶的酶活性。计算结果还表明，配体的最佳链长对于与 G-四联体实现更好的结合能力非常重要。MESP 计算和 AIM 分析证实了这些配体分子与 G-四链体结合的趋势。这些小分子中性配体具有通过被动转运穿过细胞膜的脂质双层的相当大的优势，是生物研究和临床试验的首选。
