Tetrazole-Based Probes for Integrated Phenotypic Screening, Affinity-Based Proteome Profiling, and Sensitive Detection of a Cancer Biomarker

Ke Cheng, Jun Seok Lee, Piliang Hao, Shao Q. Yao, Ke Ding, Zhengqiu Li

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15044-15048
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number47
DOIs
Publication statusPublished - 2017 Nov 20
Externally publishedYes

Keywords

  • affinity-based probes
  • cancer biomarkers
  • phenotypic screening
  • target identification
  • tetrazole

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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