Nucleic Acid Covalent Tags

The selective and site-specific chemical labeling of proteins has emerged as a pivotal research area in chemical biology and cell biology. An effective protein labeling typically meets several criteria, including high specificity, rapid and robust conjugation under physiological conditions, operation at low concentrations with biocompatibility, and minimal perturbation of the protein function and activity. The conjugation of nucleic acids with proteins has garnered significant attention recently due to the rapid advancements in nucleic acid probe technologies, leveraging the programmable nature of nucleic acids alongside the multifaceted functionalities of proteins. It helps to convert protein-specific information into nucleic acid signals, facilitating upstream versatile recognition and downstream signal amplification for the target protein. This review critically evaluates the recent progress in nucleic acid-based protein labeling methodologies, with a specific focus on covalent labeling using aptamer tags, protein fusion tags or the technique of metabolic oligosaccharide engineering. The tags establish covalent linkages with target proteins through various modalities such as small molecules or metabolic glycan engineering. The insights presented in the review highlight promising avenues for the development of highly specific and versatile protein labeling techniques, which is essential for the improvement of protein-targeted detection and imaging across diverse biological contexts.