Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural α-2,6-linked sialosides:: A P. damsela α-2,6-sialyltransferase with extremely flexible donor-substrate specificity
Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural α-2,6-linked sialosides:: A P. damsela α-2,6-sialyltransferase with extremely flexible donor-substrate specificity
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DOI：
10.1002/anie.200600572
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Chen, Xi
中科院分区：
文献类型：
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作者：
Yu, Hai;Huang, Shengsu;Chen, Xi
唾液酸是具有9个碳骨架的α-酮酸家族。它们主要作为脊椎动物糖蛋白和糖脂的末端碳水化合物单元或作为病原菌的荚膜多糖和脂寡糖的组分被发现。[1]唾液酸结构在许多重要的生理和病理过程中起着关键作用，包括细胞识别和通讯、细菌和病毒感染以及肿瘤转移等。[1]目前，在自然界中已经发现了超过50种结构不同的唾液酸形式。[1]其中，超过15种已在人类红细胞表面，唾液蛋白和胃肠道粘蛋白中发现。[2]唾液酸的三种基本形式（方案1）是N-乙酰神经氨酸（Neu 5Ac）、N-羟乙酰神经氨酸（Neu 5Gc）和脱氨基神经氨酸（KDN）。基于这三种形式，可以在C-4、C-5、C-7、C-8和/或C-9位置上的羟基处发生单个或多个取代，包括O-乙酰化和较不频繁的O-甲基化、O-乳酸化、O-硫酸化和O-磷酸化（方案2）。[1]唾液酸的修饰和修饰的唾液酸的细胞表面呈递具有物种和组织特异性。它们受发育调节，并被认为与其生物学功能密切相关。[1]然而，目前缺乏对自然界唾液酸结构多样性的机制和意义的清晰理解。这主要是由于难以获得均匀的唾液酸糖苷或唾液酸糖缀合物，特别是那些含有不同的天然存在的唾液酸修饰的唾液酸糖苷或唾液酸糖缀合物。这些结构极难从天然来源中以同质形式分离[3]，并且化学唾液酸化仍然具有挑战性。[4]虽然唾液酸转移酶催化的合成提供了很大的优势[5]，但它受到许多唾液酸转移酶的低表达水平和狭窄的底物特异性的影响，特别是来自哺乳动物来源的那些。[6]目前的化学[4，7]和酶[5，8]唾液酸化活性一直集中在含有非天然唾液酸的结构上。
Sialic acids are a family of α-keto acids with a 9-carbon backbone. They have been predominantly found as terminal carbohydrate units on glycoproteins and glycolipids of vertebrates or as components of capsular polysaccharides and lipooligosaccharides of pathogenic bacteria.[1] Sialic acid-containing structures play pivotal roles in many physiologically and pathologically important processes, including cellular recognition and communication, bacterial and viral infection, and tumor metastasis, etc.[1] Currently, greater than 50 structurally distinct forms of sialic acids have been found in nature.[1] From which, more than 15 have been found on human red blood cell surfaces, saliva proteins, and gastrointestinal mucins.[2] Three basic forms of sialic acids (Scheme 1) are N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), and deaminoneuraminc acid (KDN). Based on these three forms, single or multiple substitutions can occur at the hydroxyl group on C-4, C-5, C-7, C-8, and/or C-9 positions, including O-acetylation and the less frequent O-methylation, O-lactylation, O-sulfation, and O-phosphorylation (Scheme 2).[1]Modifications of sialic acids and cell surface presentation of modified sialic acids are speciesand tissue-specific. They are developmentally regulated and are believed to be closely related to their biological functions.[1] Nevertheless, a clear understanding of the mechanism and the significance of nature’s sialic acid structural diversity is currently missing. This is mainly due to the difficulties in obtaining homogenous sialosides or sialylglycoconjugates, especially those contain diverse naturally occurring sialic acid modifications. These structures are extremely difficult to isolate in homogenous forms from natural sources [3] and chemical sialylation remains challenging.[4] Although sialyltransferase-catalyzed synthesis offers great advantages,[5] it suffers from the low expression level and the narrow substrate specificity of many sialyltransferases, especially those from mammalian sources.[6] Current chemical [4, 7] and enzymatic [5, 8] sialylation activities have been focusing on structures containing unnatural