Yizhou Li; Guixian Zhao; Shuting Zhong; Gong Zhang; Yangfeng Li
Angew. Chem. Int. Ed. Engl., 2022, 61(7), e202115157
https://doi.org/10.1002/anie.202115157

Abstract

The use of a proper encoding methodology is one of the most important aspects when practicing DEL technology. A “headpiece”-based double-stranded DEL encoding method is currently the most widely used for productive DEL. However, the robustness of double-stranded DEL construction conflicts with the versatility presented by single-stranded DEL applications. We here report a novel encoding method, which is based on a “reversible covalent headpiece (RCHP)”. The RCHP allows reversible interconversion between double- and single-stranded DNA formats, providing an avenue to robust synthesis and allowing for the applications in distinct setups. We have validated the versatility of this encoding method with encoded self-assembled chemical library and DNA-encoded dynamic library technology. Notably, based on the RCHP-settled library construction, a unique “ternary covalent complex” mediating ligand isolation methodologies against non-immobilized targets was developed.