Chemoenzymatic Synthesis of Genetically-Encoded Multivalent Liquid N-glycan Arrays

Author:

Lin Chih-Lan1,Sojitra Mirat1ORCID,Carpenter Eric1,Hayhoe Ellen1,Sarkar Susmita1,Volker Elizabeth1,Atrazhev Alexei1,Lowary Todd1ORCID,Macauley Matthew1ORCID,Derda Ratmir1ORCID

Affiliation:

1. University of Alberta

Abstract

Abstract A hallmark of cellular glycosylation is its chemical complexity and heterogeneity, which can be challenging to capture synthetically. Using chemoenzymatic synthesis on M13 phage, we produce a genetically-encoded liquid glycan array (LiGA) of biantennary complex type N-glycans. Ligation of azido-functionalized sialylglycosyl-asparagine derived from egg yolk to phage functionalized with 50–1000 copies of dibenzocyclooctyne produced divergent intermediate that can be trimmed by glycosidases and extended by glycosyltransferases to yield a library of phages with different N-glycans. Post-reaction analysis by MALDI-TOF MS provided a rigorous approach to confirm N-glycan structure and density, both of which were encoded in the bacteriophage DNA. The binding of this N-glycan LiGA by ten lectins, including CD22 or DC-SIGN expressed on live cells, uncovered an optimal structure/density combination for recognition. Injection of the LiGA into mice identified glycoconjugates with structures and avidity necessary for enrichment in specific organs. This work provides an unprecedented quantitative evaluation of the interaction of complex N-glycans with GBPs in vitro and in vivo.

Publisher

Research Square Platform LLC

Reference71 articles.

1. Determination of glycosylation sites and site-specific heterogeneity in glycoproteins;An HJ;Curr. Opinion. Chem. Biol.,2009

2. Biological roles of glycans;Varki A;Glycobiology,2017

3. Vertebrate protein glycosylation: diversity, synthesis and function;Moremen KW;Nat. Rev. Mol. Cell Biol.,2012

4. Glycosylation in cancer: mechanisms and clinical implications;Pinho SS;Nature Reviews Cancer,2015

5. Glycosylation in health and disease;Reily C;Nat. Rev. Nephrol.,2019

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