A simple and effective biocompatible domino reaction triggered by a model protease and leading to the formation of strongly fluorescent quinoxalin-2(1)-one -heterocycles is described. Some positive attributes including versatility and the ability to provide outstanding fluorescence "OFF-ON" responses were revealed by this work. They open the way for practical applications of this novel type of "covalent-assembly"-based fluorescent probe in the fields of sensing and bioimaging.
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http://dx.doi.org/10.1021/acs.orglett.0c02287 | DOI Listing |
Chem Sci
November 2024
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University Nanjing 210046 China
Amonafide (ANF), a topoisomerase II inhibitor and DNA intercalator, has exhibited promise in phase II trials but faces significant limitations due to adverse side effects. Here, we have developed a novel enzyme-triggered fluorogenic prodrug, AcKLP, that incorporates dual-locked enzyme activation, ensuring that the prodrug remains inactive until it confronts the unique enzymatic environment of glioblastoma cells. This approach minimizes premature activation and reduces toxicity to normal cells, with an IC > 100 μM for human umbilical vein endothelial cells (HUVEC) and ∼2.
View Article and Find Full Text PDFJ Agric Food Chem
October 2024
Université d'Orléans et CNRS, ICOA, UMR 7311, BP 6759, Orléans F-45067, France.
Myrosinase, a thioglucosidase, is a key enzyme in the mechanism of defense of plants that hydrolyzes glucosinolates (GSLs) into isothiocyanates. These isothiocyanates are the main bioactive molecules exerting protective effect in Brassicales plants. These plants that contain this specific enzyme-substrate couple belong to our daily human diet and have demonstrated health benefits, such as chemopreventive effects.
View Article and Find Full Text PDFJ Mater Chem B
March 2022
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, Assam, India.
We describe herein the rational development of an organopolysulfide-based fluorogenic donor of hydrogen sulfide (HS) DCI-PS, which can be activated by the antioxidant selenoenzyme thioredoxin reductase (TrxR) with concomitant release of the dicyanoisophorone-based near-infrared (NIR) fluorophore. Along with the polysulfide probe DCI-PS capable of releasing the NIR fluorophore and HS, the corresponding disulfide-probe DCI-DS was also rationally designed and synthesized, which releases the fluorophore without donating HS. Detailed spectroscopic and kinetic studies in an aqueous medium revealed significantly higher reactivity of the probes towards DTT (for TrxR activity) over the well-known cellular abundant biothiol GSH.
View Article and Find Full Text PDFOrg Lett
August 2020
Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21000 Dijon, France.
A simple and effective biocompatible domino reaction triggered by a model protease and leading to the formation of strongly fluorescent quinoxalin-2(1)-one -heterocycles is described. Some positive attributes including versatility and the ability to provide outstanding fluorescence "OFF-ON" responses were revealed by this work. They open the way for practical applications of this novel type of "covalent-assembly"-based fluorescent probe in the fields of sensing and bioimaging.
View Article and Find Full Text PDFMethods Enzymol
June 2021
Department of Chemistry, Stony Brook University, Stony Brook, NY, United States; Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, United States. Electronic address:
Since first reported at the beginning of the 21st century, bioorthogonal reactions have become powerful tools for investigating biological systems. Here, we review several classic and current bioorthogonal reactions, including the Staudinger-Bertozzi ligation, strain-promoted azide-alkyne cycloaddition (SPAAC), 1,3-dipolar cycloaddition, and tetrazine-alkene ligation. We discuss the capabilities and limitations of the subset of current bioorthogonal reactions that can be "turned on" by exposure to light or an enzyme.
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