Wei Yu-Bai, Luo Dong, Xiong Xiao, Huang Yong-Liang, Xie Mo, Lu Weigang, Li Dan
College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University Guangzhou 510632 P. R. China
Department of Chemistry, Shantou University Medical College Shantou Guangdong 515041 P. R. China.
Chem Sci. 2022 Mar 21;13(17):4813-4820. doi: 10.1039/d2sc00188h. eCollection 2022 May 4.
DNA-protein crosslinks (DPCs) are highly toxic DNA lesions induced by crosslinking agents such as formaldehyde (HCHO). Building artificial models to simulate the crosslinking process would advance our understanding of the underlying mechanisms and therefore develop coping strategies accordingly. Herein we report the design and synthesis of a Zn-based metal-organic framework with mixed ligands of 2,6-diaminopurine and amine-functionalized dicarboxylate, representing DNA and protein residues, respectively. Combined characterization techniques allow us to demonstrate the unusual efficiency of HCHO-crosslinking within the confined space of the titled MOF. Particularly, single-crystal X-ray diffraction studies reveal a sequential methylene-knitting process upon HCHO addition, along with strong fluorescence that was not interfered with by other metabolites, glycine, and Tris. This work has successfully constructed a purine-based metal-organic framework with unoccupied Watson-Crick sites, serving as a crystalline model for HCHO-induced DPCs by mimicking the confinement effect of protein/DNA interactions.
DNA-蛋白质交联（DPCs）是由甲醛（HCHO）等交联剂诱导产生的高毒性DNA损伤。构建人工模型来模拟交联过程将有助于我们深入理解其潜在机制，从而相应地制定应对策略。在此，我们报告了一种基于锌的金属有机框架的设计与合成，该框架具有2,6-二氨基嘌呤和胺功能化二羧酸酯的混合配体，分别代表DNA和蛋白质残基。综合表征技术使我们能够证明在标题MOF的受限空间内HCHO交联具有非凡的效率。特别地，单晶X射线衍射研究揭示了添加HCHO后连续的亚甲基编织过程，以及不受其他代谢物、甘氨酸和Tris干扰的强荧光。这项工作成功构建了一个具有未占据沃森-克里克位点的嘌呤基金属有机框架，通过模拟蛋白质/DNA相互作用的限制效应，作为HCHO诱导的DPCs的晶体模型。
