Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Chembiochem. 2020 Sep 14;21(18):2696-2700. doi: 10.1002/cbic.202000226. Epub 2020 May 14.
The introduction of chemical reporter groups into glycan structures through metabolic oligosaccharide engineering (MOE) followed by bio-orthogonal ligation is an important tool to study glycosylation. We show the incorporation of synthetic galactose derivatives that bear terminal alkene groups in hepatic cells, with and without infection by Plasmodium berghei parasites, the causative agent of malaria. Additionally, we demonstrated the contribution of GLUT1 to the transport of these galactose derivatives, and observed a consistent increase in the uptake of these compounds going from naïve to P. berghei-infected cells. Finally, we used MOE to study the interplay between Plasmodium parasites and their mosquito hosts, to reveal a possible transfer of galactose building blocks from the latter to the former. This strategy has the potential to provide new insights into Plasmodium glycobiology as well as for the identification and characterization of key glycan structures for further vaccine development.
通过代谢寡糖工程(MOE)将化学报告基团引入聚糖结构,然后进行生物正交连接,是研究糖基化的重要工具。我们展示了在感染疟原虫(Plasmodium berghei)寄生虫和未感染的情况下,将带有末端烯烃基团的合成半乳糖衍生物掺入肝细胞中的情况。此外,我们证明了 GLUT1 对这些半乳糖衍生物的转运有贡献,并观察到从幼稚细胞到感染 P. berghei 的细胞,这些化合物的摄取量持续增加。最后,我们使用 MOE 研究了疟原虫与其蚊子宿主之间的相互作用,揭示了后者向前者转移半乳糖结构单元的可能途径。该策略有可能为了解疟原虫糖生物学以及鉴定和表征用于进一步疫苗开发的关键糖结构提供新的见解。