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

克氏锥虫锥鞭毛体中糖基磷脂酰肌醇锚定粘蛋白的纯化和含 α-Gal 的新糖蛋白的合成:作为可靠诊断和早期评估恰加斯病化疗结果的生物标志物的应用

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

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.

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