20210506 Lowary TL Epub

Genetically encoded multivalent liquid glycan array displayed on M13 bacteriophage

Genetically encoded multivalent liquid glycan array displayed on M13 bacteriophage

Nat Chem Biol. 2021 Jul; 17(7):806-816. Epub 2021 May 6.
doi: 10.1038/s41589-021-00788-5

閱讀文章

Sojitra M, Sarkar S, Maghera J, Rodrigues E, Carpenter EJ, Seth S, Ferrer Vinals D, Bennett NJ, Reddy R, Khalil A, Xue X, Bell MR, Zheng RB, Zhang P, Nycholat C, Bailey JJ, Ling CC, Lowary TL, Paulson JC, Macauley MS, Derda R.

摘要

The central dogma of biology does not allow for the study of glycans using DNA sequencing. We report a liquid glycan array (LiGA) platform comprising a library of DNA 'barcoded' M13 virions that display 30-1,500 copies of glycans per phage. A LiGA is synthesized by acylation of the phage pVIII protein with a dibenzocyclooctyne, followed by ligation of azido-modified glycans. Pulldown of the LiGA with lectins followed by deep sequencing of the barcodes in the bound phage decodes the optimal structure and density of the recognized glycans. The LiGA is target agnostic and can measure the glycan-binding profile of lectins, such as CD22, on cells in vitro and immune cells in a live mouse. From a mixture of multivalent glycan probes, LiGAs identify the glycoconjugates with optimal avidity necessary for binding to lectins on living cells in vitro and in vivo.