Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and full...Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and fully characterized.Protonation of the ligands and the stability of the complexes of the ligands with divalent metal ions were investigated.The trinuclear metal complexes [Cu（Ⅱ）and Zn（Ⅱ）] of the ligands were studied,as catalysts,for the transphosphorylation of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate（HPNP）.The second-order rate constants of HPNP-hydrolysis catalyzed by M3L and M3LH-1 were obtained,which indicated that Zn3LBH-1 was the most efficient catalyst among them.The proposed mechanisms included the activation of the substrate via binding to the metal ions and intramolecular nucleophilic attack by the deprotonated C2-hydroxyl of HPNP.展开更多
RNA甲基化占整个RNA修饰的60%以上,而N_(6)-甲基腺苷(N_(6)-methyladenosine,m^(6)A)修饰是人类最常见的一种RNA修饰。m^(6)A修饰对基因表达的调节至关重要,其失调与多种疾病如肿瘤相关。我们以癌症基因组图谱(The Cancer Genome Atlas,...RNA甲基化占整个RNA修饰的60%以上,而N_(6)-甲基腺苷(N_(6)-methyladenosine,m^(6)A)修饰是人类最常见的一种RNA修饰。m^(6)A修饰对基因表达的调节至关重要,其失调与多种疾病如肿瘤相关。我们以癌症基因组图谱(The Cancer Genome Atlas,TCGA)胃癌数据集中的375例患者为对象,研究了m^(6)A相关长非编码RNA(long noncoding RNAs,lncRNAs)的预后意义:先进行Pearson相关性分析,以筛选m^(6)A相关lncRNAs,然后再进行单变量Cox回归分析,确定胃癌患者的预后。确定23种m^(6)A相关lncRNAs为预后lncRNAs后,运用LASSO-Cox回归方法,在TCGA胃癌数据集中构建m^(6)A相关lncRNAs(包括9种m^(6)A相关预后lncRNAs)预后模型。通过计算相关风险评分,并根据风险评分的中位值将胃癌患者分为低、高风险亚组。生存分析曲线和受试者操作特征曲线显示,此预后模型能对胃癌患者的预后进行可靠的预测。本研究揭示了m^(6)A RNA甲基化调节剂在胃癌发生发展中的重要性,并建立了一种m^(6)A基因表达分类模型,该模型可以令人满意地预测胃癌的预后。展开更多
基金Supported by the National Natural Science Foundation of China(Nos.20371028and20671052).
文摘Two multidentate ligands 2,9-di[6＇-（2″-hydroxyl-3″-methoxyphenyl）-n-2＇,5＇-diazahexyl]-1,10-phenanthroline（LA）and 2,9-di（6＇-α-phenol-n-2＇,5＇-diazahexyl）-1,10-phenanthroline（LB）were synthesized and fully characterized.Protonation of the ligands and the stability of the complexes of the ligands with divalent metal ions were investigated.The trinuclear metal complexes [Cu（Ⅱ）and Zn（Ⅱ）] of the ligands were studied,as catalysts,for the transphosphorylation of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate（HPNP）.The second-order rate constants of HPNP-hydrolysis catalyzed by M3L and M3LH-1 were obtained,which indicated that Zn3LBH-1 was the most efficient catalyst among them.The proposed mechanisms included the activation of the substrate via binding to the metal ions and intramolecular nucleophilic attack by the deprotonated C2-hydroxyl of HPNP.
