title: Target identification with quantitative activity based protein profiling (ABPP).
abstract: As many small bioactive molecules fulfill their functions through interacting with protein targets, the identification of such targets is crucial in understanding their mechanisms of action (MOA) and side effects. With technological advancements in target identification, it has become possible to accurately and comprehensively study the MOA and side effects of small molecules. While small molecules with therapeutic potential were derived solely from nature in the past, the remodeling and synthesis of such molecules have now been made possible. Presently, while some small molecules have seen successful application as drugs, the majority remain undeveloped, requiring further understanding of their MOA and side effects to fully tap into their potential. Given the typical promiscuity of many small molecules and the complexity of the cellular proteome, a high-flux and high-accuracy method is necessary. While affinity chromatography approaches combined with MS have had successes in target identification, limitations associated with nonspecific results remain. To overcome these complications, quantitative chemical proteomics approaches have been developed including metabolic labeling, chemical labeling, and label-free methods. These new approaches are adopted in conjunction with activity-based protein profiling (ABPP), allowing for a rapid process and accurate results. This review will briefly introduce the principles involved in ABPP, then summarize current advances in quantitative chemical proteomics approaches as well as illustrate with examples how ABPP coupled with quantitative chemical proteomics has been used to detect the targets of drugs and other bioactive small molecules including natural products.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, P. R., China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yin Kwan
authors.initials: YK
authors.lastname: Wong
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, P. R., China.|Department of Biological Sciences, National University of Singapore, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore.
authors.forename: Jigang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, P. R., China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Yew-Mun
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, P. R., China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D002846:Chromatography, Affinity; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D011506:Proteins
keywords: Activity-based protein profiling (ABPP); Biomedicine; Natural products; Quantitative chemical proteomics; Small molecules; Target identification