Neuroactive Chondroitin Sulfate Glycomimetics

We report the generation of chondroitin sulfate (CS) glycomimetics with tunable chemical and biological properties. Our approach greatly simplifies the synthesis of complex glycosaminoglycans, providing synthetically accessible, bioactive structures of programmable sulfation sequence. Using these glycopolymers, we demonstrate that multivalent interactions are critical for modulating CS activity and discover an unexpected tolerance for unnatural polymeric architectures. We envision that these glycomimetics will facilitate further explorations into the influence of macromolecular structure on glycosaminoglycan function and provide powerful tools for manipulating CS activity in vivo.