Harnessing Chemistry to Understand the Roles of Glycans in Neuroplasticity

The field of chemical neurobiology is providing insights into the molecules and interactions involved in neuronal development, sensory perception, and memory. This seminar will describe our efforts to understand the structure-function relationships of glycosaminoglycans (GAGs) and how they contribute to neuroplasticity – the ability of the brain to adapt and form new neural connections. Using a combination of synthetic organic chemistry, biochemistry, computational chemistry, cell biology, and neurobiology, we have developed a diverse set of chemical tools for studying the biology of GAGs. I will discuss a new platform for synthesizing large heparan sulfate (HS) oligosaccharide libraries displaying comprehensive arrays of sulfation patterns. These diverse structures provide insights into the elusive ‘sulfation code’ of GAGs and highlight interesting parallels to DNA recognition. Our studies also indicate that particular sulfation motifs on chondroitin sulfate (CS) glycosaminoglycans regulate signaling events that underlie processes such as axon regeneration, synaptic plasticity, and neural circuit formation. The ability to identify and modulate these sulfation motifs opens up new opportunities for neuronal regeneration and repair after stroke, central nervous system injury, and neurodegenerative diseases.