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糖基化人干扰素-γ 的全合成。

Total Synthesis of Glycosylated Human Interferon-γ.

机构信息

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

Org Lett. 2020 Sep 4;22(17):6863-6867. doi: 10.1021/acs.orglett.0c02401. Epub 2020 Aug 24.

DOI:10.1021/acs.orglett.0c02401
PMID:32830985
Abstract

Interferon-γ (IFN-γ) is a glycoprotein that is responsible for orchestrating numerous critical immune induction and modulation processes and is used clinically for the treatment of a number of diseases. Herein, we describe the total chemical synthesis of homogeneously glycosylated variants of human IFN-γ using a tandem diselenide-selenoester ligation-deselenization strategy in the C- to N-terminal direction. The synthetic glycoproteins were successfully folded, and the structures and antiviral functions were assessed.

摘要

干扰素-γ(IFN-γ)是一种糖蛋白,负责协调许多关键的免疫诱导和调节过程,并在临床上用于治疗多种疾病。在此,我们描述了使用 C 到 N 端方向的串联二硒键-硒酯连接-去硒化策略对人 IFN-γ 的均一糖基化变体进行全化学合成。合成的糖蛋白成功折叠,并评估了其结构和抗病毒功能。

相似文献

1
Total Synthesis of Glycosylated Human Interferon-γ.糖基化人干扰素-γ 的全合成。
Org Lett. 2020 Sep 4;22(17):6863-6867. doi: 10.1021/acs.orglett.0c02401. Epub 2020 Aug 24.
2
Molecular modeling of the effects of glycosylation on the structure and dynamics of human interferon-gamma.聚糖对人干扰素 - γ结构和动力学影响的分子建模。
J Mol Model. 2019 Apr 25;25(5):127. doi: 10.1007/s00894-019-4013-8.
3
The application of HPLC/MS analysis with a multi-enzyme digest strategy to characterize different interferon product variants produced from Pichia pastoris.采用 HPLC/MS 分析与多酶消化策略相结合,用于表征毕赤酵母生产的不同干扰素产品变体。
Amino Acids. 2019 Sep;51(9):1353-1363. doi: 10.1007/s00726-019-02772-9. Epub 2019 Aug 24.
4
Role of N-glycosylation in the synthesis, dimerization and secretion of human interferon-gamma.N-糖基化在人γ-干扰素合成、二聚化及分泌中的作用
Biochem J. 1994 Nov 1;303 ( Pt 3)(Pt 3):831-40. doi: 10.1042/bj3030831.
5
Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma.人干扰素-γ生物活性单链突变体的设计、表征及结构
J Mol Biol. 2000 May 26;299(1):169-79. doi: 10.1006/jmbi.2000.3734.
6
N-glycosylation of human interferon-gamma: glycans at Asn-25 are critical for protease resistance.人γ干扰素的N-糖基化:天冬酰胺-25处的聚糖对蛋白酶抗性至关重要。
Biochem J. 1995 May 15;308 ( Pt 1)(Pt 1):9-14. doi: 10.1042/bj3080009.
7
The Chemical Synthesis of Site-Specifically Modified Proteins Via Diselenide-Selenoester Ligation.通过二硒键-硒酯键连接的定点修饰蛋白质的化学合成。
Methods Mol Biol. 2021;2355:231-251. doi: 10.1007/978-1-0716-1617-8_18.
8
Recombinant human interferon-gamma. Differences in glycosylation and proteolytic processing lead to heterogeneity in batch culture.重组人干扰素-γ。糖基化和蛋白水解加工的差异导致分批培养中的异质性。
Biochem J. 1990 Dec 1;272(2):333-7. doi: 10.1042/bj2720333.
9
Biosynthesis and N-glycosylation of human interferon-gamma. Asn25 and Asn97 differ markedly in how efficiently they are glycosylated and in their oligosaccharide composition.人γ干扰素的生物合成与N-糖基化。天冬酰胺25和天冬酰胺97在糖基化效率及其寡糖组成方面存在显著差异。
Eur J Biochem. 1996 Dec 1;242(2):191-200. doi: 10.1111/j.1432-1033.1996.0191r.x.
10
The glycosylation heterogeneity of recombinant human IFN-gamma.重组人干扰素-γ的糖基化异质性
J Interferon Cytokine Res. 1998 May;18(5):287-95. doi: 10.1089/jir.1998.18.287.

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