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1
Purification of Glycosylphosphatidylinositol-Anchored Mucins from Trypanosoma cruzi Trypomastigotes and Synthesis of α-Gal-Containing Neoglycoproteins: Application as Biomarkers for Reliable Diagnosis and Early Assessment of Chemotherapeutic Outcomes of Chagas Disease.从克氏锥虫锥鞭毛体中纯化糖基磷脂酰肌醇锚定粘蛋白并合成含α-半乳糖的新糖蛋白:作为恰加斯病可靠诊断和化疗结果早期评估生物标志物的应用
Methods Mol Biol. 2019;1955:287-308. doi: 10.1007/978-1-4939-9148-8_22.
2
Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN-gamma-primed-macrophages.从克氏锥虫锥鞭毛体中分离出的糖基磷脂酰肌醇锚定的黏蛋白样糖蛋白,可诱导体内白细胞募集,这一过程依赖于干扰素-γ预处理的巨噬细胞产生单核细胞趋化蛋白-1。
J Leukoc Biol. 2002 May;71(5):837-44.
3
A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.一种分支和双α-半乳糖结合的合成糖蛋白作为恰加斯病的生物标志物。
Molecules. 2022 Sep 5;27(17):5714. doi: 10.3390/molecules27175714.
4
Synthesis of Galα(1,3)Galβ(1,4)GlcNAcα-, Galβ(1,4)GlcNAcα- and GlcNAc-containing neoglycoproteins and their immunological evaluation in the context of Chagas disease.α-半乳糖(1,3)β-半乳糖(1,4)N-乙酰葡糖胺、β-半乳糖(1,4)N-乙酰葡糖胺和含N-乙酰葡糖胺的新糖蛋白的合成及其在恰加斯病背景下的免疫学评估。
Glycobiology. 2016 Jan;26(1):39-50. doi: 10.1093/glycob/cwv081. Epub 2015 Sep 18.
5
Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and potentiated by IFN- γ and CD40-CD40L interactions.克氏锥虫诱导人外周血单核细胞产生白细胞介素-12是由糖基磷脂酰肌醇锚定的粘蛋白样糖蛋白介导的,并由干扰素-γ和CD40-CD40L相互作用增强。
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Glycosylphosphatidylinositol-anchored mucin-like glycoproteins from Trypanosoma cruzi bind to CD1d but do not elicit dominant innate or adaptive immune responses via the CD1d/NKT cell pathway.来自克氏锥虫的糖基磷脂酰肌醇锚定的黏蛋白样糖蛋白与CD1d结合,但不会通过CD1d/NKT细胞途径引发主要的先天性或适应性免疫反应。
J Immunol. 2002 Oct 1;169(7):3926-33. doi: 10.4049/jimmunol.169.7.3926.
7
An α-Gal antigenic surrogate as a biomarker of treatment evaluation in Trypanosoma cruzi-infected children. A retrospective cohort study.α-半乳糖抗原替代标志物用于评价感染克氏锥虫儿童的治疗效果:一项回顾性队列研究。
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8
Use of Trypanosoma cruzi purified glycoprotein (GP57/51) or trypomastigote-shed antigens to assess cure for human Chagas' disease.使用克氏锥虫纯化糖蛋白(GP57/51)或锥鞭毛体脱落抗原评估人类恰加斯病的治愈情况。
Am J Trop Med Hyg. 1993 Nov;49(5):625-35. doi: 10.4269/ajtmh.1993.49.625.
9
Lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas' disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi.来自慢性恰加斯病患者的溶细胞性抗α-半乳糖基抗体可识别克氏锥虫黏蛋白样糖基磷脂酰肌醇锚定糖蛋白上的新型O-连接寡糖。
Biochem J. 1994 Dec 15;304 ( Pt 3)(Pt 3):793-802. doi: 10.1042/bj3040793.
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A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease.一种来自克氏锥虫粘蛋白样相关表面蛋白的合成肽作为抗恰加斯病疫苗的候选物。
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Mol Pharm. 2025 May 5;22(5):2623-2638. doi: 10.1021/acs.molpharmaceut.5c00034. Epub 2025 Apr 9.
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An α-Gal antigenic surrogate as a biomarker of treatment evaluation in Trypanosoma cruzi-infected children. A retrospective cohort study.α-半乳糖抗原替代标志物用于评价感染克氏锥虫儿童的治疗效果:一项回顾性队列研究。
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Big is not better: Comparing two alpha-Gal-bearing glycotopes in neoglycoproteins as biomarkers for Leishmania (Viannia) braziliensis infection.大并不一定好:比较两种作为 Leishmania (Viannia) braziliensis 感染生物标志物的α-Gal 结合糖肽在糖肽中的作用。
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A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease.一种分支和双α-半乳糖结合的合成糖蛋白作为恰加斯病的生物标志物。
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Screening and Identification of Metacaspase Inhibitors: Evaluation of Inhibition Mechanism and Trypanocidal Activity.筛选和鉴定 Metacaspase 抑制剂:抑制机制和抗锥虫活性评估。
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The Glycan Structure of mucins Depends on the Host. Insights on the Chameleonic Galactose.粘蛋白的聚糖结构取决于宿主。关于变色龙半乳糖的新见解。
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本文引用的文献

1
Course of serological tests in treated subjects with chronic Trypanosoma cruzi infection: A systematic review and meta-analysis of individual participant data.治疗后慢性克氏锥虫感染患者的血清学检测结果:一项个体参与者数据的系统评价和荟萃分析。
Int J Infect Dis. 2018 Aug;73:93-101. doi: 10.1016/j.ijid.2018.05.019. Epub 2018 Jun 4.
2
Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.使用苯硝唑和三种 E1224 给药方案治疗成人慢性不定型恰加斯病:概念验证、随机、安慰剂对照试验。
Lancet Infect Dis. 2018 Apr;18(4):419-430. doi: 10.1016/S1473-3099(17)30538-8. Epub 2018 Jan 16.
3
Access to benznidazole for Chagas disease in the United States-Cautious optimism?在美国,治疗恰加斯病的苯硝唑可及性——谨慎的乐观态度?
PLoS Negl Trop Dis. 2017 Sep 14;11(9):e0005794. doi: 10.1371/journal.pntd.0005794. eCollection 2017 Sep.
4
Chagas disease.恰加斯病。
Lancet. 2018 Jan 6;391(10115):82-94. doi: 10.1016/S0140-6736(17)31612-4. Epub 2017 Jun 30.
5
Synthesis of Galα(1,3)Galβ(1,4)GlcNAcα-, Galβ(1,4)GlcNAcα- and GlcNAc-containing neoglycoproteins and their immunological evaluation in the context of Chagas disease.α-半乳糖(1,3)β-半乳糖(1,4)N-乙酰葡糖胺、β-半乳糖(1,4)N-乙酰葡糖胺和含N-乙酰葡糖胺的新糖蛋白的合成及其在恰加斯病背景下的免疫学评估。
Glycobiology. 2016 Jan;26(1):39-50. doi: 10.1093/glycob/cwv081. Epub 2015 Sep 18.
6
Old and new challenges in Chagas disease.恰加斯病的新旧挑战。
Lancet Infect Dis. 2015 Nov;15(11):1347-56. doi: 10.1016/S1473-3099(15)00243-1. Epub 2015 Jul 28.
7
Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives.慢性恰加斯病治疗反应的生物标志物:现状与未来展望
Mem Inst Oswaldo Cruz. 2015 May;110(3):422-32. doi: 10.1590/0074-02760140435. Epub 2015 Apr 28.
8
Chagas disease in Latin America: an epidemiological update based on 2010 estimates.拉丁美洲的恰加斯病:基于2010年估计数的流行病学最新情况。
Wkly Epidemiol Rec. 2015 Feb 6;90(6):33-43.
9
Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives.慢性恰加斯病病因治疗的近期临床试验:进展、挑战与展望
J Eukaryot Microbiol. 2015 Jan-Feb;62(1):149-56. doi: 10.1111/jeu.12184. Epub 2014 Nov 13.
10
Evaluation of a chemiluminescent enzyme-linked immunosorbent assay for the diagnosis of Trypanosoma cruzi infection in a nonendemic setting.在非流行地区评估一种用于诊断克氏锥虫感染的化学发光酶联免疫吸附测定法。
Mem Inst Oswaldo Cruz. 2013 Nov;108(7):928-31. doi: 10.1590/0074-0276130112.

从克氏锥虫锥鞭毛体中纯化糖基磷脂酰肌醇锚定粘蛋白并合成含α-半乳糖的新糖蛋白:作为恰加斯病可靠诊断和化疗结果早期评估生物标志物的应用

Purification of Glycosylphosphatidylinositol-Anchored Mucins from Trypanosoma cruzi Trypomastigotes and Synthesis of α-Gal-Containing Neoglycoproteins: Application as Biomarkers for Reliable Diagnosis and Early Assessment of Chemotherapeutic Outcomes of Chagas Disease.

作者信息

Ortega-Rodriguez Uriel, Portillo Susana, Ashmus Roger A, Duran Jerry A, Schocker Nathaniel S, Iniguez Eva, Montoya Alba L, Zepeda Brenda G, Olivas Janet J, Karimi Nasim H, Alonso-Padilla Julio, Izquierdo Luis, Pinazo Maria-Jesús, de Noya Belkisyolé Alarcón, Noya Oscar, Maldonado Rosa A, Torrico Faustino, Gascon Joaquim, Michael Katja, Almeida Igor C

机构信息

Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.

Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, TX, USA.

出版信息

Methods Mol Biol. 2019;1955:287-308. doi: 10.1007/978-1-4939-9148-8_22.

DOI:10.1007/978-1-4939-9148-8_22
PMID:30868536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6589430/
Abstract

Chagas disease (ChD), caused by the protozoan parasite Trypanosoma cruzi, affects millions of people worldwide. Chemotherapy is restricted to two drugs, which are partially effective and may cause severe side effects, leading to cessation of treatment in a significant number of patients. Currently, there are no biomarkers to assess therapeutic efficacy of these drugs in the chronic stage. Moreover, no preventive or therapeutic vaccines are available. In this chapter, we describe the purification of Trypanosoma cruzi trypomastigote-derived glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI-mucins) for their use as antigens for the reliable primary or confirmatory diagnosis and as prognostic biomarkers for early assessment of cure following ChD chemotherapy. We also describe, as an example, the synthesis of a potential tGPI-mucin-derived α-Gal-terminating glycan and its coupling to a carrier protein for use as diagnostic and prognostic biomarker in ChD.

摘要

恰加斯病(ChD)由原生动物寄生虫克氏锥虫引起,影响着全球数百万人。化疗仅限于两种药物,它们部分有效且可能会引起严重的副作用,导致大量患者停止治疗。目前,尚无生物标志物可用于评估这些药物在慢性期的治疗效果。此外,也没有预防性或治疗性疫苗。在本章中,我们描述了克氏锥虫滋养体衍生的糖基磷脂酰肌醇(GPI)锚定粘蛋白(tGPI-粘蛋白)的纯化方法,这些粘蛋白用作抗原可用于可靠的初步或确诊诊断,以及作为预后生物标志物用于恰加斯病化疗后治愈情况的早期评估。我们还举例描述了一种潜在的tGPI-粘蛋白衍生的α-半乳糖末端聚糖的合成及其与载体蛋白的偶联,用作恰加斯病的诊断和预后生物标志物。

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