Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, United States.
Department of Medicine, University of California, San Diego, California 92093, United States.
J Org Chem. 2021 Nov 5;86(21):14381-14397. doi: 10.1021/acs.joc.1c01091. Epub 2021 Oct 12.
A novel chemoenzymatic synthon strategy has been developed to construct a comprehensive library of α2-3- and α2-6-linked sialosides containing 7-- or 7,9-di--acetyl sialic acid, the stable analogue of naturally occurring 7--acetyl- or 7,9-di--acetyl-sialic acid. Diazido and triazido-mannose derivatives that were readily synthesized chemically from inexpensive galactose were shown to be effective chemoenzymatic synthons. Together with bacterial sialoside biosynthetic enzymes with remarkable substrate promiscuity, they were successfully used in one-pot multienzyme (OPME) sialylation systems for highly efficient synthesis of sialosides containing multiple azido groups. Conversion of the azido groups to -acetyl groups generated the desired sialosides. The hydrophobic and UV-detectable benzyloxycarbonyl (Cbz) group introduced in the synthetic acceptors of sialyltransferases was used as a removable protecting group for the propylamine aglycon of the target sialosides. The resulting -acetyl sialosides were novel stable probes for sialic acid-binding proteins such as plant lectin MAL II, which bond strongly to sialyl T antigens with or without an -acetyl at C7 or at both C7 and C9 in the sialic acid.
一种新的化学酶联合合成策略被开发出来，用于构建包含 7--或 7,9-二--乙酰神经氨酸的 α2-3-和 α2-6-连接唾液酸的综合文库，7--乙酰基或 7,9-二--乙酰神经氨酸是天然存在的稳定类似物。从廉价的半乳糖化学合成的叠氮和三氮基甘露糖衍生物被证明是有效的化学酶联合合成物。与具有显著底物混杂性的细菌唾液酸生物合成酶一起，它们被成功地用于一锅多酶（OPME）唾液酸化系统中，以高效合成含有多个叠氮基团的唾液酸。将叠氮基团转化为 -乙酰基基团生成所需的唾液酸。唾液酸转移酶合成受体中引入的疏水性和可紫外检测的苄氧羰基（Cbz）基团被用作目标唾液酸的丙胺糖苷配基的可移动保护基团。得到的 -乙酰基唾液酸是新型稳定的唾液酸结合蛋白探针，如植物凝集素 MAL II，它与带有或不带有 C7 上的 -乙酰基或 C7 和 C9 上的 -乙酰基的唾液酰 T 抗原强烈结合。
