Louçano João, Both Peter, Marchesi Andrea, Del Bino Linda, Adamo Roberto, Flitsch Sabine, Salwiczek Mario
GlycoUniverse GmbH & Co KGaA Am Mühlenberg 11 14476 Potsdam Germany
School of Chemistry, University of Manchester, Manchester Institute of Biotechnology 131 Princess Street Manchester M1 7DN UK.
RSC Adv. 2020 Jun 22;10(40):23668-23674. doi: 10.1039/d0ra01803a. eCollection 2020 Jun 19.
is a major human pathogen with increasing antibiotic resistance. Pneumococcal vaccines consist of capsular polysaccharide (CPS) or their related fragments conjugated to a carrier protein. The repeating unit of type 14 CPS shares a core structure with the CPS of Group B (GBS) type III: the only difference is that the latter exhibits a sialic acid unit, with a α-2,3 linkage to galactose. Here, the automated glycan assembly (AGA) of two frameshifts of the repeating unit of type 14 is described. The same strategy is used to assemble dimers of the different repeating unit frameshifts. The four structures are assembled with only three commercially available monosaccharide building blocks. We also report an example of how enzymatic sialylation of the compounds obtained with AGA completes a synthetic route for GBS type III glycans. The synthesized structures were tested in competitive ELISA and further confirmed the branched tetrasaccharide Gal-Glc-(Gal-)GlcNAc to be the minimal epitope of type 14.
是一种抗生素耐药性不断增加的主要人类病原体。肺炎球菌疫苗由与载体蛋白偶联的荚膜多糖（CPS）或其相关片段组成。14型CPS的重复单元与B组（GBS）III型CPS具有共同的核心结构：唯一的区别是后者表现出一个唾液酸单元，与半乳糖以α-2,3键连接。在此，描述了14型重复单元的两个移码的自动聚糖组装（AGA）。使用相同的策略组装不同重复单元移码的二聚体。这四种结构仅用三种市售单糖构建块组装而成。我们还报告了一个例子，即通过AGA获得的化合物的酶促唾液酸化如何完成GBS III型聚糖的合成路线。合成的结构在竞争性ELISA中进行了测试，并进一步证实分支四糖Gal-Glc-(Gal-)GlcNAc是14型的最小表位。
