Kangyin Pan; Ying Yao; Yiyuan Zhang; Yuang Gu; Yan Wang; Peixiang Ma; Wei Hou; Guang Yang; Shuning Zhang; Hongtao Xu
Bioconjugate Chem., 2023, 34(8), 1459-1466
https://doi.org/10.1021/acs.bioconjchem.3c00235

Abstract

The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate–azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles. Thus, it will not only further enrich the DEL chemistry toolbox but also will have great potential in practical DEL synthesis.