糖辅助组辅助以多样性为导向的酶模块化合成0系列甘化甘的酶模块化合成
Jinfeng Ye1,2,3, Kan Zhong1,2, Zhi-Fei Hu1,2
1Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Angewandte Chemie (International ed. in English)
|December 23, 2024
概括
研究人员开发了一种新型的酶方法来合成复杂的0系列化物. 这种方法克服了以前的局限性,通过使用酸作为临时辅助组,使得可以创建扩展的化物结构.
科学领域:
- 葡萄糖生物学 葡萄糖生物学
- 酶合成酶的合成
- 碳水化合物化学 碳水化合物化学
背景情况:
- 扩展的0系列类酶的酶合成受到了关键酶如β1-4-N-乙烯基酸氨基转移酶无法直接延长糖链的限制.
- 现有的方法难以创建具有延伸脊柱的复杂的氏体结构.
研究的目的:
- 开发一种新型的酶策略,用于合成扩展的0系列化物核心结构.
- 为了克服Campylobacter jejuni β1-4-N-乙烯基银胺基转移酶 (CjCgtA) 的基质特异性限制.
- 为了生成复杂的0系列化物的一系列图书馆.
主要方法:
- 酶介绍酸作为辅助组,以促进甘氨酸链的延长.
- 使用来自Photobacterium damselae (Pd2,6ST) 的细菌α2-6-sialyltransferase,具有特定的受体基质特性.
- 采用序列酶模块组件组件来实现化体结构的多样化.
- 在适当的阶段使用sianlidase去除 sialic 酸辅助组.
主要成果:
- 通过克服CjCgtA的局限性,成功合成了扩展的0系列类固醇核心结构.
- 鉴定了一种细菌基转移酶 (Pd2,6ST),它对0系列类核具有意想不到的特异性.
- 通过模块化组装生成了31个复杂的0系列类甘氨酸库.
- 在复杂的甘氨酸合成中证明了酸作为可移除的辅助组的实用性.
结论:
- 开发的酶策略使得以前无法获得的扩展的0系列化物合成成为可能.
- 使用酸作为辅助组是克服酶特异性挑战的可行方法.
- 这种方法提供了一个强大的平台,用于生成多样化和复杂的化体结构,以便进一步研究.
相关概念视频
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Protein Glycosylation
6.8K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.8K
Biosynthesis of Polysaccharides
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K


