Abnormal cell surface glycosylation plays a major role in disease processes such as immune evasion, however, the underlying the role of glycans is yet to be properly understood. The information obtained from a glycan array has been a critical starting point for downstream applications such as development of inhibitors, carbohydrate vaccines, and therapeutics. However, the progress in elucidating the role of glycans has suffered due to the lack of 1:1 correspondence between DNA and glycan structures. It is challenging to use powerful techniques of DNA deep sequencing to analyze glycan recognition. We developed Liquid Glycan Array (LiGA) technology that allows for genetically encoding glycans. LiGA provides a 1:1 correspondence between the glycan displayed in multiple copies on a bacteriophage carrier and the DNA sequence inside the phage. Each phage virion displays 30-1500 copies of glycan to reproduce critical variables in glycan recognition: valency and spatial presentation. LiGA is synthesized by acylation of phage pVIII protein with a dibenzocyclooctyne, followed by ligation of azido-modified glycans. A simple pulldown of the LiGA along with lectins followed by deep sequencing of the DNA in the bound phages decodes the recognized glycans. LiGA is target agnostic and measures binding profile of lectins expressed on intact cells, such as CD22 and DC-SIGN (Nat. Chem. Bio. 17, 806–816, 2021). From a mixture of 50-100 multivalent glycan probes, LiGA can identify the glycan-phage conjugates with optimal valency and spatial presentation for binding to antibodies and lectins on cells in vitro and in vivo.

Genetically encoded multivalent liquid glycan array displayed on M13 bacteriophage

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.