Biomimetic mimicry of formaldehyde-induced DNA-protein crosslinks in the confined space of a metal-organic framework

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. Her...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2022-05, Vol.13 (17), p.4813-482
Main Authors: Wei, Yu-Bai, Luo, Dong, Xiong, Xiao, Huang, Yong-Liang, Xie, Mo, Lu, Weigang, Li, Dan
Format: Article
Language:English
Subjects:
Biomimetics
Chemistry
Confined spaces
Crosslinking
Crystals
Formaldehyde
Glycine
Knitting
Metabolites
Metal-organic frameworks
Mimicry
Proteins
Single crystals
Zinc
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Summary: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, in situ 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. An amine-functionalized biological metal-organic framework serving as a crystalline model for mimicking formaldehyde-induced DNA-protein crosslinks in a confined space.
ISSN:2041-6520
2041-6539
DOI:10.1039/d2sc00188h