Self-Immobilizing Quinone Methides for the Fluorescent Sensing of Enzyme Activity

Abstract

Gaining insight into biological processes relies on sensitive analytical techniques. These often require labeling of biomolecules that help visualize them. Selective covalent labeling without preliminary modification of the biomolecules is an advantageous method. For example, this can be achieved by using probes that are capable of in situ quinone methide (QM) formation. The QM can be masked to give a stable precursor, and the highly reactive form is only generated upon activation by a specific trigger. The in situ formed QM then binds covalently to the nucleophilic side chains of either the target protein or a protein in close proximity. Using fluorogenic probes further improves this method by reducing non-specific background signals, thus improving signal-to-noise ratios. In this review we summarize the development of quinone methide-based probes from mechanism-based inactivation to red-emitting, fluorogenic activity probes, focusing on enzyme-triggered activation.

Arylcyanomethylenequinone Oximes: An Overview of Synthesis, Chemical Transformations, and Biological Activity

“…To the best knowledge of the authors of this review, there is an absence of a professional literature review discussing arylcyanomethylenequinone oximes in detail. Several papers dedicated to the specific types of quinone methides put their focus on the generation of quinone methide core and its reactivity [ 46 ], on the application of quinone methides in asymmetric organocatalysis [ 47 ], on their biological properties [ 48 , 49 ], and potential application, e.g., in the fluorescent sensing of enzymatic activity [ 50 ]. The polycyclic friedelane-type triterpenoid quinone methides [ 51 ] and pyridinium quinone methide derivatives [ 52 ] are also known to be biologically active.…”