Modular Click Assembly DNA-Encoded Glycoconjugate Libraries with on-DNA Functional Group Transformations
Xing Yi Ling, Sixiu Liu, Yixuan Yang, Qian Dong, Lisa A. Marcaurelle, Weitong Huang, Yun Ding, Xuan Wang, Xiaojie Lu
Abstract
Carbohydrates are an important class of naturally active products and play vital roles in regulating various physiological activities. To meet the demand for carbohydrate-based libraries used for the identification of potential drug candidates for pharmaceutical-related targets, we developed a set of on-DNA protocols to construct the DNA-encoded glycoconjugates, including Seyferth-Gilbert homologation, anomeric azidation, and CuAAC cyclization. These on-DNA chemistries enable the generation and modification of DNA-linked glycosyl compounds with good conversions and broad substrate scope. Finally, three DNA-linked glycoconjugate libraries were successfully generated to demonstrate their applicability and feasibility in library preparation.