Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk, Egypt.
Nat Chem Biol. 2021 Jul;17(7):806-816. doi: 10.1038/s41589-021-00788-5. Epub 2021 May 6.
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.
生物学的中心法则不允许使用 DNA 测序来研究聚糖。我们报告了一种液体糖链阵列（LiGA）平台，该平台包含一个 DNA“条形码”M13 噬菌体文库，每个噬菌体展示 30-1500 个糖链拷贝。LiGA 通过用二苯并环辛炔酰化噬菌体 pVIII 蛋白，然后连接叠氮修饰的聚糖来合成。用凝集素拉下 LiGA，然后对结合的噬菌体中的条形码进行深度测序，可解码出识别聚糖的最佳结构和密度。LiGA 是靶标不可知的，可测量细胞外的凝集素（如 CD22）的聚糖结合谱，以及活体小鼠中的免疫细胞。从混合的多价糖链探针中，LiGAs 确定了与体外和体内活细胞上的凝集素结合所需的最佳亲和力的糖缀合物。
