Glycosylated biopolymers are ubiquitous in living systems but remain difficult to study through traditional biochemical approaches. Synthetic glycopolymers are promising as tools to study glycobiology and could prove translationally useful as ligands for lectin receptors. However, work in the field has generally focused on relatively-short oligopeptides or non-native polymer backbones due to practical synthetic considerations. To address this limitation, we reported the transition metal-initiated N-carboxyanhydride (NCA) polymerization of N-acetylgalactosamine-serine polypeptides as mucin mimics, creating a precedent for the synthesis of low-polydispersity O-linked glycosylated polypeptides by this strategy. Here, we explored an alternative application of our platform by synthesizing a panel of immunostimulatory glycopeptides bearing canonical pathogen-associated carbohydrates. Disaccharide- and trisaccharide-serine NCAs proved to be competent monomers, demonstrating that the technology is compatible with higher-order oligosaccharides. Azide-bearing catalysts allowed us to create polymers featuring an N-terminal amine and C-terminal azide for additional functionalization. Using this highly-modular approach, we were able to probe how glycosylation density, sugar composition, polymer length, and conjugation to various substrates impact immune cell activity in a variety of model systems.

Probing innate immunity with tunable synthetic glycopeptides

253rd National Meeting (2017)

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