N‐Carboxyanhydride Polymerization of Glycopolypeptides That Activate Antigen‐Presenting Cells through Dectin‐1 and Dectin‐2

Abstract The C‐type lectins dectin‐1 and dectin‐2 contribute to innate immunity against microbial pathogens by recognizing their foreign glycan structures. These receptors are promising targets for vaccine development and cancer immunotherapy. However, currently available agonists are heterogeneous glycoconjugates and polysaccharides from natural sources. Herein, we designed and synthesized the first chemically defined ligands for dectin‐1 and dectin‐2. They comprised glycopolypeptides bearing mono‐, di‐, and trisaccharides and were built through polymerization of glycosylated N ‐carboxyanhydrides. Through this approach, we achieved glycopolypeptides with high molecular weights and low dispersities. We identified structures that elicit a pro‐inflammatory response through dectin‐1 or dectin‐2 in antigen‐presenting cells. With their native proteinaceous backbones and natural glycosidic linkages, these agonists are attractive for translational applications.