Science of Synthesis

Cai, B.; Krusemark, C. J., Science of Synthesis: DNA-Encoded Libraries, (2024) 1, 604.

The methodology described here utilizes covalent crosslinking or enzymatic proximity tagging to select DELs against membrane-protein targets on live cells. While the crosslinking approach is accessible and readily adoptable, there are some limitations, such as low DNA recovery. The enzyme-mediated proximity labeling approach improves ligand recovery by capitalizing on the power of enzymatic turnover. In addition, recombinant expression of a target protein is still required. Further development of the enzymatic tagging protocols are underway to explore alternative enzymatic tags for proximity labeling, such as APEX[‌13‌] and miniSOG,[‌14‌] as well as a photo-deprotection labeling approach using a photo-protected affinity label and a luciferase protein tag.[‌15‌]

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