Semi‐Synthetic Sialic Acid Probes for Challenging the Substrate Promiscuity of Enzymes in the Sialoconjugation Pathway,Advanced Synthesis & Catalysis

当前位置： X-MOL 学术 › Adv. Synth. Catal. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Semi‐Synthetic Sialic Acid Probes for Challenging the Substrate Promiscuity of Enzymes in the Sialoconjugation Pathway
Advanced Synthesis & Catalysis ( IF 4.4 ) Pub Date : 2020-09-18 , DOI: 10.1002/adsc.202000859
Alexander Mertsch ₁ , Silvan Poschenrieder ₁ , Wolf-Dieter Fessner ₁

Affiliation

A series of unusual sialic acid analogs were prepared using a semi‐synthetic strategy. Truncation of natural N‐acetylneuraminic acid was followed by diastereoselective carbon backbone reconstruction using Barbier‐type carboligations as well as different functional group interconversions, which provided access to a variety of functional motifs in the terminal carbon backbone, including examples of saturated and unsaturated, linear and branched alkyl chains, partially deoxygenated sialic acids, sialic diacids and a first truncated legionaminic acid analog. The synthetic sialic acid probes were studied for nucleotide activation by the CMP‐sialic acid synthetase from Neisseria meningitidis using a universal pH‐shift assay for kinetic analysis. One‐pot enzymatic nucleotide activation and sialyltransfer to lactose was performed using a selection of five probes together with an engineered α2,3‐sialyltransferase from Photobacterium phosphoreum to furnish five new‐to‐nature analogs of the GM3 trisaccharide, which were finally utilized to test the substrate tolerance of two bacterial sialidases. The obtained set of sialic acid analogs and neo‐sialocojugates provides interesting opportunities for further glycobiology studies.

中文翻译：

半合成唾液酸探针，用于挑战唾液结合途径中底物酶的混杂性

使用半合成策略制备了一系列不同寻常的唾液酸类似物。截断天然N-乙酰神经氨酸后，使用Barbier型羰基化以及不同的官能团互变，进行非对映选择性碳骨架的重建，这提供了对末端碳骨架中各种功能基序的访问，包括饱和和不饱和，线性支链烷基链，部分脱氧的唾液酸，唾液酸二酸和第一个截短的军团胺酸类似物。通过脑膜炎奈瑟氏菌的CMP-唾液酸合成酶研究了合成唾液酸探针的核苷酸激活使用通用的pH位移测定进行动力学分析。一锅酶促核苷酸活化和唾液酸基转移至乳糖的方法是使用五种探针进行选择，并结合来自磷酸杆菌的工程改造的α2,3-唾液酸基转移酶，以提供GM3三糖的五种新近的类似物，最终将其用于测试两种细菌唾液酸酶的底物耐受性。获得的一组唾液酸类似物和新唾液酸共轭物为进一步的糖生物学研究提供了有趣的机会。

更新日期：2020-09-18

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11