Recent advances in glycoprotein synthesis

YANG Haoran; YE Farong; HUANG Ping; WANG Ping

doi:10.12211/2096-8280.2024-018

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Recent advances in glycoprotein synthesis

Invited Review | 更新时间：2025-03-19

- Recent advances in glycoprotein synthesis
- Synthetic Biology Journal Vol. 5, Issue 5, Pages: 1072-1101(2024)
- 作者机构：
  
  1.上海交通大学化学化工学院，张江高等研究院，糖化学生物学中心，变革性分子前沿科学中心，上海市手性药物分子工程重点实验室，上海 200240
  2.上海交通大学四川研究院，四川成都 610218
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-018
  CLC： Q816
- Received：04 February 2024，
  
  Revised：2024-03-20，
  
  Published：31 October 2024
- 稿件说明：
移动端阅览
杨皓然，叶发荣，黄平，王平. 糖蛋白合成的研究进展［J］. 合成生物学， 2024， 5（5）： 1072-1101

YANG Haoran， YE Farong， HUANG Ping， WANG Ping. Recent advances in glycoprotein synthesis［J］. Synthetic Biology Journal， 2024， 5（5）： 1072-1101
杨皓然，叶发荣，黄平，王平. 糖蛋白合成的研究进展［J］. 合成生物学， 2024， 5（5）： 1072-1101 DOI： 10.12211/2096-8280.2024-018.

YANG Haoran， YE Farong， HUANG Ping， WANG Ping. Recent advances in glycoprotein synthesis［J］. Synthetic Biology Journal， 2024， 5（5）： 1072-1101 DOI： 10.12211/2096-8280.2024-018.

摘要

糖基化修饰在各类生理活动中起着非常关键的作用。然而，天然糖蛋白中糖型结构的微观异质性，严重阻碍了糖型结构与糖蛋白功能之间构效关系的研究。因此，从分子层面精确控制糖蛋白结构的化学合成方法是解决这一难题的重要手段。随着蛋白质合成和糖工程技术的不断进步，研究者们发展多种蛋白质连接策略和糖苷键构建策略来精确合成均质糖蛋白。本综述将从化学、酶法构建糖苷键的角度梳理现有的糖蛋白全合成以及结合生物表达方法的半合成策略，分别介绍这些策略在合成带有

-糖基化、

-糖基化修饰等不同糖基化类型的复杂均质糖蛋白时所取得的成果，例如带有多个复杂

-糖基化修饰的HSV gD和含有长疏水片段的IL-2；以及运用这些合成的复杂糖蛋白了解糖基化修饰在各项生理过程中的构效关系所作出的突破，例如抗原糖蛋白中糖链长短与免疫原性的关系、

-GlcNAc调节神经元突触功能的机制等。最后总结了现有合成策略在糖苷键构建、纯化策略、蛋白溶解度等方面取得的进展，并指出选择性和合成产率的进一步优化仍是糖蛋白合成领域亟待解决的问题，而糖蛋白合成技术在开发免疫疗法以及理解各种疾病分子机理等方面的广泛应用，从理解原理到开发产品方面拓展了合成科学在生

命健康领域的发展方向。

Abstract

Glycosylation modifications

extensively present on the surfaces of eukaryotic proteins as a type of post-translational modification

hold significant physiological and pathological implications. The microscopic heterogeneity of natural glycoproteins has led to the emergence of the chemical synthesis of homogeneous glycoproteins with defined structures as a crucial frontier in exploring the structure-function relationships of glycosylation modifications. With the flourishing development of protein synthesis and glycoengineering technologies

various protein ligation and polysaccharide synthesis strategies have been developed

enabling the preparation of glycoproteins containing hundreds of amino acid residues. The development of glycoprotein synthesis strategies primarily revolves around chemical and enzymatic approaches for glycosidic bond formation

leading to effective synthesis schemes such as Lansbury’s aspartic acid acylation

chemical strategies based on glycosyl amino acid building blocks

and glycan remodeling strategies using endoglycosidases and glycosyltransferases. This review will discuss the chemical and enzymatic construction of glycosidic bonds

examining existing strategies for the total synthesis of glycoproteins and semi-synthetic approaches that combine with biological expression methods. It will introduce these strategies’ achievements in synthesizing complex homogeneous glycoproteins with different types of glycosylation modifications

such as those with multiple complex

-glycosylation modifications like HSV gD and those containing long hydrophobic segments like IL-2. Additionally

this review will highlight breakthroughs in understanding the structure-function relationships of glycosylation modifications in various physiological processes through these synthetic complex glycoproteins

including the relationship between glycan chain length and immunogenicity in antigenic glycoproteins

d the mechanisms by which

-GlcNAc regulates synaptic function in neurons. Finally

it will summarize the progress made in glycosidic bond construction

purification strategies

and protein solubility

and point out that further optimization of selectivity and synthetic yield remains a pressing issue in the field of glycoprotein synthesis. The wide application of glycoprotein synthesis technology in developing immunotherapies and understanding the molecular mechanisms of various diseases expands the development directions of synthetic science in the field of life and health

from understanding principles to developing products.

关键词

Keywords

references

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