Chemoenzymatic Synthesis of DSGb5 and Sialylated Globo‐series Glycans

• Published in: Angewandte Chemie 2019-08, Vol.131 (33), p.11395-11400
• Main Authors: Li, Pei‐Jhen, Huang, Szu‐Yu, Chiang, Pei‐Yun, Fan, Chen‐Yo, Guo, Li‐Jhen, Wu, Dung‐Yeh, Angata, Takashi, Lin, Chun‐Cheng
• Format: Article
• Language: English
• Subjects: Affinity; Binding; Chemistry; DSGb5; Enzymatische Synthese; Galactose; Glycan; Mikroarrays; Natural killer cells; Polysaccharides; Sialinsäure; Siglec-7-Lectin; Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201903943

Sialic‐acid‐binding, immunoglobulin‐type lectin‐7 (Siglec‐7) is present on the surface of natural killer cells. Siglec‐7 shows preference for disialylated glycans, including α(2,8)‐α(2,3)‐disialic acids or internally branched α(2,6)‐NeuAc, such as disialosylglobopentaose (DSGb5). Herein, DSGb5 was synthesized by a one‐pot multiple enzyme method from Gb5 by α2,3‐sialylation (with PmST1) followed by α2,6‐sialylation (with Psp2,6ST) in 23 % overall yield. DSGb5 was also chemoenzymatically synthesized. The protection of the nonreducing‐end galactose of Gb5 as 3,4‐O‐acetonide, 3,4‐O‐benzylidene, and 4,6‐O‐benzylidene derivatives provided DSGb5 in overall yields of 26 %, 12 %, and 19 %, respectively. Gb3, Gb4, and Gb5 were enzymatically sialylated to afford a range of globo‐glycans. Surprisingly, DSGb5 shows a low affinity for Siglec‐7 in a glycan microarray binding affinity assay. Among the synthesized globo‐series glycans, α6α3DSGb4 shows the highest binding affinity for Siglec‐7. Synthese geglykt: Glykane der Sialyl‐globo‐Serie, darunter DSGb5 und Sialylgloboside, wurden durch eine Eintopfsynthese unter Verwendung mehrerer Enzyme sowie eine chemoenzymatische Synthese hergestellt. Die erhaltenen Glykane wurden mithilfe eines Glykan‐Mikroarray‐basierten Bindungsassays bezüglich ihrer Bindung an Sialinsäure‐bindendes Lectin‐7 vom Immunglobulintyp (Siglet‐7) durchmustert.