中国科学院上海药物研究所李铁海团队开发简化复杂糖肽液相组装的综合化学酶方法。相关研究成果发表在2022年5月11日出版的国际学术期刊《美国化学会杂志》。

蛋白质的糖基化是一种复杂的翻译后修饰。尽管糖蛋白组学取得了重大进展，但由于难以获得均一的糖肽或糖蛋白，糖蛋白的准确功能仍不明确。

该文中，研究人员描述了一种通过整合疏水标签支持的化学合成和酶糖基化来制备复杂糖肽的简化化学酶方法。疏水性标签用于促进液相中肽链的延伸和产品的快速分离。在去除标签后，通过高效的糖基转移酶催化反应将一系列聚糖安装在肽上。这种方法的普遍适用性和稳健性通过高效制备16种定义明确的SARS-CoV-2 O-糖肽、4种复合MUC1糖肽和31-聚体糖基化胰高血糖素样肽-1得到了证明。

开发的方法将为方便获得各种具有生物重要性的复杂糖肽开辟一个新的途径。

附：英文原文

Title: Integrated Chemoenzymatic Approach to Streamline the Assembly of Complex Glycopeptides in the Liquid Phase

Author: Wenjing Ma, Yaqi Deng, Zhuojia Xu, Xingbang Liu, Digantkumar G. Chapla, Kelley W. Moremen, Liuqing Wen, Tiehai Li

Issue&Volume: May 11, 2022

Abstract: Glycosylation of proteins is a complicated post-translational modification. Despite the significant progress in glycoproteomics, accurate functions of glycoproteins are still ambiguous owing to the difficulty in obtaining homogeneous glycopeptides or glycoproteins. Here, we describe a streamlined chemoenzymatic method to prepare complex glycopeptides by integrating hydrophobic tag-supported chemical synthesis and enzymatic glycosylations. The hydrophobic tag is utilized to facilitate peptide chain elongation in the liquid phase and expeditious product separation. After removal of the tag, a series of glycans are installed on the peptides via efficient glycosyltransferase-catalyzed reactions. The general applicability and robustness of this approach are exemplified by efficient preparation of 16 well-defined SARS-CoV-2 O-glycopeptides, 4 complex MUC1 glycopeptides, and a 31-mer glycosylated glucagon-like peptide-1. Our developed approach will open up a new range of easy access to various complex glycopeptides of biological importance.

DOI: 10.1021/jacs.2c01819

Source: https://pubs.acs.org/doi/10.1021/jacs.2c01819