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Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-05-22 , DOI: 10.1039/d0md00122h
Anutthaman Parthasarathy 1 , Karunakaran Kalesh 2
Affiliation  

Mass spectrometry-based proteomics enables accurate measurement of the modulations of proteins on a large scale upon perturbation and facilitates the understanding of the functional roles of proteins in biological systems. It is a particularly relevant methodology for studying Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei, as the gene expression in these parasites is primarily regulated by posttranscriptional mechanisms. Large-scale proteomics studies have revealed a plethora of information regarding modulated proteins and their molecular interactions during various life processes of the protozoans, including stress adaptation, life cycle changes and interactions with the host. Important molecular processes within the parasite that regulate the activity and subcellular localisation of its proteins, including several co- and post-translational modifications, are also accurately captured by modern proteomics mass spectrometry techniques. Finally, in combination with synthetic chemistry, proteomic techniques facilitate unbiased profiling of targets and off-targets of pharmacologically active compounds in the parasites. This provides important data sets for their mechanism of action studies, thereby aiding drug development programmes.

中文翻译:

击败锥虫三重奏:导致被忽视的热带病的原生动物寄生虫的蛋白质组学

基于质谱的蛋白质组学能够在扰动时大规模准确测量蛋白质的调节,并有助于理解蛋白质在生物系统中的功能作用。它是研究利什曼原虫、克氏锥虫布氏锥虫的一种特别相关的方法,因为这些寄生虫中的基因表达主要受转录后机制调节。大规模蛋白质组学研究揭示了有关原生动物各种生命过程中调节蛋白及其分子相互作用的大量信息,包括应激适应、生命周期变化以及与宿主的相互作用。现代蛋白质组学质谱技术也可以准确捕获寄生虫内调节其蛋白质的活性和亚细胞定位的重要分子过程,包括几种共翻译和翻译后修饰。最后,与合成化学相结合,蛋白质组学技术有助于对寄生虫中药理活性化合物的靶标和脱靶进行公正的分析。这为其作用机制研究提供了重要的数据集,从而有助于药物开发计划。
更新日期:2020-06-24
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