Systematic Evaluation\nof Macromolecular Carbohydrate-Lectin\nRecognition Using Precision Glycopolymers

The\nprecise modulation of protein-carbohydrate interactions is\ncritical in glycobiology, where multivalent binding governs key cellular\nprocesses. As such, synthetic glycopolymers are useful for probing\nthese interactions. Herein, we developed precision glycopolymers (PGPs)\nwith unambiguous local chemical composition and well-defined global\nstructure and systematically evaluated the effect of polymer length,\nhydrophobicity, and backbone hybridization as well as glycan density\nand identity on the binding to both mammalian and plant lectins. Our\nstudies identified glycan density as a critical factor, with PGPs\nbelow 50% grafting density showing significantly weaker lectin interactions.\nCoarse-grained molecular dynamics simulations suggest that the observed\nphenomena may be due to a decrease in carbohydrate-carbohydrate interactions\nin fully grafted PGPs, leading to improved solvent accessibility.\nIn functional assays, these PGPs reduced the cell viability and migration\nin 4T1 breast cancer cells. Our findings establish a structure–activity\nrelationship in glycopolymers, providing new strategies for designing\nsynthetic glycomacromolecules for a myriad of applications.