Department of Chemistry, National Tsing Hua University, 101, Sec. 2, Kuang Fu Rd., Hsinchu, 30013, Taiwan.
Institute of Biological Chemistry, Academia Sinica, 128, Sec. 2, Academia Rd., Nankang, Taipei, 11529, Taiwan.
Angew Chem Int Ed Engl. 2019 Aug 12;58(33):11273-11278. doi: 10.1002/anie.201903943. Epub 2019 Jul 4.
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.
唾液酸结合免疫球蛋白型凝集素 7（Siglec-7）存在于自然杀伤细胞的表面。Siglec-7 对二唾液酸化糖具有偏好性，包括α(2,8)-α(2,3)-二唾液酸或内部分支的α(2,6)-NeuAc，如二唾液酰基Globopentaose（DSGb5）。本文通过一锅多酶法，从 Gb5 通过α2,3-唾液酸化（用 PmST1），然后通过α2,6-唾液酸化（用 Psp2,6ST），以 23%的总收率得到 DSGb5。DSGb5 也通过化学酶法合成。Gb5 的非还原端半乳糖的 3,4-O-乙酰基、3,4-O-亚苄基和 4,6-O-亚苄基保护基分别以 26%、12%和 19%的总收率提供 DSGb5。Gb3、Gb4 和 Gb5 被酶促唾液酸化，得到一系列Globoglycans。令人惊讶的是，在糖芯片结合亲和力测定中，DSGb5 对 Siglec-7 的亲和力较低。在合成的 Globoside 系列糖中，α6α3DSGb4 对 Siglec-7 具有最高的结合亲和力。
