Yuhan Gui; Clara Shania Wong; Guixian Zhao; Chao Xie; Rui Hou; Yizhou Li; Gang Li; Xiaoyu Li
ACS Omega, 2022, 7(13), 11491-11500
https://doi.org/10.1021/acsomega.2c01152

Abstract

DNA-encoded library (DEL) is an efficient high-throughput screening technology platform in drug discovery and is also gaining momentum in academic research. Today, the majority of DELs are assembled and encoded with double-stranded DNA tags (dsDELs) and has been selected against numerous biological targets; however, dsDELs are not amendable to some of the recently developed selection methods, such as the cross-linking-based selection against immobilized targets and live-cell-based selections, which require DELs encoded with single-stranded DNAs (ssDELs). Herein, we present a simple method to convert dsDELs to ssDELs using exonuclease digestion without library redesign and resynthesis. We show that dsDELs could be efficiently converted to ssDELs and used for affinity-based selections either with purified proteins or on live cells.