Zhaomei Sun; Ying Zhong; Yahui Chen; Lingqian Xiao; Jiangying Wang; Fanming Zeng; Kexin Yang; Nicolas Duchemin; Yun Jin Hu
Org. Lett., 2024, XXXX, XXX, XXX-XXX
https://doi.org/10.1021/acs.orglett.4c01138

Abstract

DNA-encoded library (DEL) technologies enable the fast exploration of gigantic chemical space to identify ligands for the target protein of interest and have become a powerful hit finding tool for drug discovery projects. However, amenable DEL chemistry is restricted to a handful of reactions, limiting the creativity of drug hunters. Here, we describe a new on-DNA synthetic pathway to access sulfides and sulfoximines. These moieties, usually contemplated as challenging to achieve through alkylation and oxidation, can now be leveraged in routine DEL selection campaigns.