Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Instituto de Medicina Molecular João Lobo Antunes, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
ChemMedChem. 2022 Jul 19;17(14):e202200174. doi: 10.1002/cmdc.202200174. Epub 2022 May 19.
Activity-based protein profiling (ABPP) is an approach used at the interface of chemical biology and proteomics that uses small molecular probes to provide dynamic fingerprints of enzymatic activity in complex proteomes. Malaria is a disease caused by Plasmodium parasites with a significant death burden and for which new therapies are actively being sought. Here, we compile the main achievements from ABPP studies in malaria and highlight the probes used and the different downstream platforms for data analysis. ABPP has excelled at studying Plasmodium cysteine proteases and serine hydrolase families, the targeting of the proteasome and metabolic pathways, and in the deconvolution of targets and mechanisms of known antimalarials. Despite the major impact in the field, many antimalarials and enzymatic families in Plasmodium remain to be studied, which suggests ABPP will be an evergreen technique in the field.
基于活性的蛋白质组学分析（ABPP）是一种化学生物学和蛋白质组学交叉领域的方法，它使用小分子探针为复杂蛋白质组中的酶活性提供动态指纹图谱。疟疾是一种由疟原虫引起的疾病，它造成了巨大的死亡负担，目前正在积极寻找新的治疗方法。在这里，我们汇编了疟疾中 ABPP 研究的主要成果，并强调了所使用的探针以及不同的下游数据分析平台。ABPP 在研究疟原虫半胱氨酸蛋白酶和丝氨酸水解酶家族、蛋白酶体和代谢途径的靶向以及已知抗疟药物的靶点和作用机制的解析方面表现出色。尽管在该领域产生了重大影响，但仍有许多抗疟药物和疟原虫中的酶家族有待研究，这表明 ABPP 将成为该领域的一项常青技术。
