Glycopolymer Microarrays with Sub‐Femtomolar Avidity for Glycan Binding Proteins Prepared by Grafted‐To/Grafted‐From Photopolymerizations

We report a novel glycan array architecture that binds the mannose‐specific glycan binding protein, concanavalin A (ConA), with sub‐femtomolar avidity. A new radical photopolymerization developed specifically for this application combines the grafted‐from thiol–(meth)acrylate polymerization with thiol–ene chemistry to graft glycans to the growing polymer brushes. The propagation of the brushes was studied by carrying out this grafted‐to/grafted‐from radical photopolymerization (GTGFRP) at >400 different conditions using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization on surfaces. The effect of brush height and the grafting density of mannosides on the binding of ConA to the brushes was studied systematically, and we found that multivalent and cooperative binding account for the unprecedented sensitivity of the GTGFRP brushes. This study further demonstrates the ease with which new chemistry can be tailored for an application as a result of the advantages of hypersurface photolithography. Sub‐femtomolar avidity with glycan binding protein is achieved in a glycan microarray architecture that controls precisely carbohydrate density and valency. The biomimetic glycopolymers are prepared via a new surface‐initiated polymerization, termed „grafted‐to/grafted‐from radical photopolymerization“ that was optimized using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization.