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Tetrazole‐Based Probes for Integrated Phenotypic Screening, Affinity‐Based Proteome Profiling, and Sensitive Detection of a Cancer Biomarker
Author(s) -
Cheng Ke,
Lee JunSeok,
Hao Piliang,
Yao Shao Q.,
Ding Ke,
Li Zhengqiu
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201709584
Subject(s) - proteome , biomarker discovery , phenotypic screening , computational biology , biomarker , phenotype , drug discovery , profiling (computer programming) , cancer cell , biology , small molecule , cancer , cancer research , proteomics , bioinformatics , biochemistry , genetics , computer science , gene , operating system
Abstract Target‐identification phenotypic screening has been a powerful approach in drug discovery; however, it is hindered by difficulties in identifying the underlying cellular targets. To address this challenge, we have combined phenotypic screening of a fully functionalized small‐molecule library with competitive affinity‐based proteome profiling to map and functionally characterize the targets of screening hits. Using this approach, we identified ANXA2, PDIA3/4, FLAD1, and NOS2 as primary cellular targets of two bioactive molecules that inhibit cancer cell proliferation. We further demonstrated that a panel of probes can label and/or image annexin A2 (a cancer biomarker) from different cancer cell lines, thus providing opportunities for potential cancer diagnosis and therapy.