Formyl Functionalized Nucleic Acids: A Versatile Tool for Epigenetic and Biomolecules Detection in Nucleic Acids

Formyl-functionalized oligonucleotides have attracted the attention of researchers worldwide due to their high reactivity, easy postsynthetic modifications, diverse transformations, and efficient labeling or cross-linking with various biomolecules. In DNA, the modified bases 5-formylcytosine and 5-formyluracil act not only as important epigenetic markers but also as reactive groups that can form covalent DNA-protein cross-links through Schiff base chemistry. Such interactions may cause DNA damage, influence gene expression, and trigger other biological effects. This review outlines current strategies for detecting 5-formylcytosine and 5-formyluracil in DNA, with particular emphasis on fluorescence labeling using organic probes and the identification of biomolecules via DNA-protein crosslink formation. By summarizing these approaches, we aim to provide readers with practical insights into their applications in chemical biology and biomedical research. Looking forward, further refinement of these methods could enable more precise disease diagnostics and open new opportunities for therapeutic development.