Recent advances in proteome-wide label-free target deconvolution for bioactive small molecules

Sun, Jichao1,2,3,4; Prabhu, Nayana5; Tang, Jun1,2,6; Yang, Fan3,4,6; Jia, Lin7; Guo, Jinan1,2; Xiao, Kefeng1,2; Tam, Wai Leong8,9,10,11; Nordlund, Par5,12; Dai, Lingyun1,2,3,4,5

2021-02-01

10.1002/med.21788

MEDICINAL RESEARCH REVIEWS   影响因子和分区

0198-6325

1098-1128

Small-molecule drugs modulate biological processes and disease states through engagement of target proteins in cells. Assessing drug-target engagement on a proteome-wide scale is of utmost importance in better understanding the molecular mechanisms of action of observed beneficial and adverse effects, as well as in developing next generation tool compounds and drugs with better efficacies and specificities. However, systematic assessment of drug-target engagement has been an arduous task. With the continuous development of mass spectrometry-based proteomics instruments and techniques, various chemical proteomics approaches for drug target deconvolution (i.e., the identification of molecular target for drugs) have emerged. Among these, the label-free target deconvolution approaches that do not involve the chemical modification of compounds of interest, have gained increased attention in the community. Here we provide an overview of the basic principles and recent biological applications of the most important label-free methods including the cellular thermal shift assay, pulse proteolysis, chemical denaturant and protein precipitation, stability of proteins from rates of oxidation, drug affinity responsive target stability, limited proteolysis, and solvent-induced protein precipitation. The state-of-the-art technical implications and future outlook for the label-free approaches are also discussed.

drug target deconvolution label‐ free methodology mass spectrometry molecular mechanism of action proteomics

SCI

英语

通讯

National Natural Science Foundation of China[32070748,82003814,81902787] ; National Medical Research Council["NMRC/CIRG/1470/2017","NMRC/OFIRG/0064/2017","NMRC/OFLCG/002-2018","OFIRG19nov-0106"] ; National Research Foundation Singapore["CRP23-2019-0024","NRF-CRP22-2019-0003"]

Pharmacology & Pharmacy

Chemistry, Medicinal ; Pharmacology & Pharmacy

WOS:000614091000001

WILEY

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Urol, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Urol Minimally Invas Engn Ctr, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Geriatr, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China
5.ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore
6.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou, Guangdong, Peoples R China
7.Shenzhen Technol Univ, Coll Pharm, Shenzhen, Guangdong, Peoples R China
8.ASTAR, Genome Inst Singapore, Singapore 138672, Singapore
9.Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore
10.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore
11.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore
12.Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden

Sun, Jichao,Prabhu, Nayana,Tang, Jun,et al. Recent advances in proteome-wide label-free target deconvolution for bioactive small molecules[J]. MEDICINAL RESEARCH REVIEWS,2021.

Sun, Jichao.,Prabhu, Nayana.,Tang, Jun.,Yang, Fan.,Jia, Lin.,...&Dai, Lingyun.(2021).Recent advances in proteome-wide label-free target deconvolution for bioactive small molecules.MEDICINAL RESEARCH REVIEWS.

Sun, Jichao,et al."Recent advances in proteome-wide label-free target deconvolution for bioactive small molecules".MEDICINAL RESEARCH REVIEWS (2021).