Glyco-IEG: Sequence- and Stereo-Defined Macromolecules towards Selective Lectin Binding

Presenter: 

Manuel Hartweg

Authors: 

Manuel Hartweg,1‡ Yivan Jiang,1‡ Gökhan Yilmaz, Cassie Jarvis,1 Hung V. T. Nguyen,1 Gastón A. Primo,2 Alessandra Monaco,2 Valentin P. Beyer,2 Alvaro Mata,2 Kathleen Chen,1 Laura L. Kiessling,1 Jeremiah A. Johnson,1 and C. Remzi Becer,2

Author Affiliation: 

1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States 2. Polymer Chemistry Laboratory, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, E1 4NS London, UK

Abstract: 

Lectins have been found to be key biological units that are responsible for signal transmission and local intercellular communication. They accomplish these responsibilities through recognition of oligosaccharides that are either solubilized or embedded on the surfaces of bacteria, plant cells, animal cells, and viruses. Many of the precise mechanisms and signalling pathways that lectins control are directly related to different diseases and triggers in the immune system; thus, there is a great desire to specifically stimulate therapeutic lectins for targeted therapy. This targeting is unfortunately complicated to accomplish without unintentionally triggering other undesired lectin signalling pathways. Oligosaccharides, the natural lectin substrates, accomplish this through their extremely nuanced structures: each saccharide monomer alone has countless variations in anomeric centers, ring sizes, linkages, site specific substitutions, and branch points. To take control over the vast biological functions of lectins and use them in the therapeutic setting, we need to better understand the important structural parameters of their sugar-based molecule substrates. Therefore, we designed a strategy for the synthesis of stereo-controlled, unimolecular glycopolymers with different architectures. These glycopoylmers can be manipulated to preferentially bind specific lectins. In addition to confirming increased valency increases overall binding strength of our glycopolymers to lectins, we have found that different stereoconfigurations and macromolecular architecture (linear vs. cyclic) bias glycopolymers towards binding different lectins. Finally, by changing the mannose side chain to a phenylmannose side chain, we are able to further change the physical properties of our glycopolymer system and the resulting biological effects. These initial proofs of concept demonstrate the structural versatility of our IEG synthesized polytriazole platforms, and with our reported findings, we aim to further develop the glycopolymer field and eventually create novel, efficacious lectin targeting pharmaceuticals.