A Cofactor‐Substrate‐Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions. Issue 15 (21st February 2020)

• Record Type: Journal Article
• Authors: Jiao, Yang; Zhang, Lei; Gao, Xu; Si, Wen; Duan, Chunying
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 15(2020)
• Page Start: 6021
• Page End: 6027
• Publication Date: 2020-02-21
• Subjects: cofactor mimics -- enzymes -- hypoxia -- metal–organic capsules -- supramolecular chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201915040
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early‐stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L‐NO2, within the NADH mimic‐containing metal–organic capsule Zn‐MPB, we developed a cofactor‐substrate‐based supramolecular luminescent probe for ultrafast detection of hypoxia‐related enzymes in solution in vitro and in vivo. The host–guest structure fuses the coenzyme and substrate into one supramolecular probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double‐substrate mechanism to a single‐substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra‐molecular pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation. Abstract : Caged cofactors : A cofactor‐substrate‐based supramolecular probe strategy for ultrafast (within seconds) and quantitative detection of nitroreductase under hypoxic conditions is proposed. The probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra‐molecular pathway with increased activity.