Centro di Servizio di Ateneo per le Scienze e Tecnologie per la Vita (CESTEV), University of Napoli Federico II, Via Tommaso De Amicis 95, 80145 Napoli, Italy.
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127 Trieste, Italy.
Molecules. 2024 Nov 19;29(22):5446. doi: 10.3390/molecules29225446.
Herein, we report the structure-based selection via molecular docking of four -heterocyclic bis-carbene gold(I) complexes, whose potential as ligands for the hTel23 G-quadruplex structure has been investigated using circular dichroism (CD) spectroscopy, CD melting, and polyacrylamide gel electrophoresis (PAGE). The complex containing a bis(1,2,3,4,6,7,8,9-octahydro-11-11-pyridazino[1,2-a]indazol-11-yl) scaffold induces a transition from the hybrid (3 + 1) topology to a prevalent parallel G-quadruplex conformation, whereas the complex featuring a bis(2-(2-acetamidoethyl)-3-imidazo[1,5-a]pyridin-3(2)-yl) moiety disrupted the original G-quadruplex structure. These results deserve particular attention in light of the recent findings on the pathological involvements of G-quadruplexes in neurodegenerative diseases.
在此，我们通过分子对接从四个杂环双卡宾金（I）配合物中进行基于结构的选择，使用圆二色性（CD）光谱、CD 熔融和聚丙烯酰胺凝胶电泳（PAGE）研究了它们作为 hTel23 G-四链体结构配体的潜力。含有双（1,2,3,4,6,7,8,9-八氢-11-11-吡咯嗪[1,2-a]吲哚-11-基）支架的配合物诱导从混合（3+1）拓扑结构到主要的平行 G-四链体构象的转变，而具有双（2-（2-乙酰氨基乙基）-3-咪唑并[1,5-a]吡啶-3（2）-基）部分的配合物破坏了原始的 G-四链体结构。鉴于最近发现 G-四链体在神经退行性疾病中的病理参与，这些结果值得特别关注。
