Decoding Glycan Molecular Recognition: From Chemical Principles to Neuroplasticity
Glycosaminoglycans (GAGs) mediate critical molecular recognition events that regulate diverse biological processes, ranging from development and immune responses to neuroplasticity and disease. We have developed a platform for the chemical synthesis and biological interrogation of large heparan sulfate (HS) oligosaccharide libraries encompassing diverse sulfation patterns. These libraries enable the identification of sulfation sequences that selectively modulate the activities of growth factors, chemokines, and other signaling proteins, revealing new insights into the elusive "sulfation code" of GAGs and striking parallels with DNA molecular recognition. Deciphering and engineering glycan molecular recognition provides new opportunities to control cell signaling, promote neuroplasticity, and inspire new diagnostic and therapeutic strategies.