Directing GDNF-mediated neuronal signaling with proactively programmable cell-surface saccharide-free glycosaminoglycan mimeticsElectronic supplementary information (ESI) available: Experimental details, compound characterization, and supporting tables, figures and schemes. See DOI: 10.1039/c8cc09253b

A significant barrier to harnessing the power of cell-surface glycosaminoglycans (GAGs) to modulate glial cell-line-derived neurotrophic factor (GDNF) signaling is the difficulty in accessing key GAG structures involved. Here, we report tailored GDNF signaling using synthetic polyproline-based GAG mimetics (PGMs). PGMs deliver the much needed proactive programmability for GDNF recognition and effectively modulate GDNF-mediated neuronal processes in a cellular context. We report tailorable glycocalyx engineering where {Z} 12 imparts the recruitment of GDNF to the cell surface and promotes GDNF-mediated neuronal differentiation.