Target Enzyme-Activated Two-Photon Fluorescent Probes: A Case Study of CYP3A4 Using a Two-Dimensional Design Strategy

Jing Ning, Wei Wang, Guangbo Ge, Peng Chu, Feida Long, Yongliang Yang, Yulin Peng, Lei Feng, Xiaochi Ma, Tony D. James

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The rapid development of fluorescent probes for monitoring target enzymes is still a great challenge owing to the lack of efficient ways to optimize a specific fluorophore. Herein, a practical two-dimensional strategy was designed for the development of an isoform-specific probe for CYP3A4, a key cytochrome P450 isoform responsible for the oxidation of most clinical drugs. In first dimension of the design strategy, a potential two-photon fluorescent substrate (NN) for CYP3A4 was effectively selected using ensemble-based virtual screening. In the second dimension, various substituent groups were introduced into NN to optimize the isoform-selectivity and reactivity. Finally, with ideal selectivity and sensitivity, NEN was successfully applied to the real-time detection of CYP3A4 in living cells and zebrafish. These findings suggested that our strategy is practical for developing an isoform-specific probe for a target enzyme.

Original languageEnglish
Pages (from-to)9959-9963
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number29
Early online date17 May 2019
DOIs
Publication statusPublished - 15 Jul 2019

Keywords

  • analytical methods
  • cytochrome P450 3A4
  • enzyme-activatable probes
  • fluorescent probes
  • molecular design

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Target Enzyme-Activated Two-Photon Fluorescent Probes : A Case Study of CYP3A4 Using a Two-Dimensional Design Strategy. / Ning, Jing; Wang, Wei; Ge, Guangbo; Chu, Peng; Long, Feida; Yang, Yongliang; Peng, Yulin; Feng, Lei; Ma, Xiaochi; James, Tony D.

In: Angewandte Chemie - International Edition, Vol. 58, No. 29, 15.07.2019, p. 9959-9963.

Research output: Contribution to journalArticle

Ning, Jing ; Wang, Wei ; Ge, Guangbo ; Chu, Peng ; Long, Feida ; Yang, Yongliang ; Peng, Yulin ; Feng, Lei ; Ma, Xiaochi ; James, Tony D. / Target Enzyme-Activated Two-Photon Fluorescent Probes : A Case Study of CYP3A4 Using a Two-Dimensional Design Strategy. In: Angewandte Chemie - International Edition. 2019 ; Vol. 58, No. 29. pp. 9959-9963.
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