A multi-branched fluorogenic probe for the rapid and specific detection of Gram-negative bacteria is reported. Three Gram-negative-targeting azido-modified polymyxins were clicked onto a trivalent scaffold functionalised with the environmental green-emitting fluorophore 7-nitrobenz-2-oxa-1,3-diazole. The probe allowed wash-free detection of target bacteria with increased sensitivity and lower limits of detection compared to monovalent probes.
View Article and Find Full Text PDFThe ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBN, a construct that readily expresses from E.
View Article and Find Full Text PDFCathepsin D is a protease that is an effector in the immune response of macrophages, yet to date, only a limited number of probes have been developed for its detection. Herein, we report a water soluble, highly sensitive, pH insensitive fluorescent probe for the detection of Cathepsin D activity that provides a strong OFF/ON signal upon activation and with bright emission at 515 nm. The probe was synthesised using a combination of solid and solution-phase chemistries, with probe optimisation to increase its water solubility and activation kinetics by addition of a long PEG chain (5 kDa) at the C-terminus.
View Article and Find Full Text PDFProteases are excellent biomarkers for a variety of diseases, offer multiple opportunities for diagnostic applications and are valuable targets for therapy. From a chemistry-based perspective this review discusses and critiques the most recent advances in the field of substrate-based probes for the detection and analysis of proteolytic activity both and
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