Funding opportunities in Chemical Biology, Trinity College Dublin.

Activity-Based Probes (ABPs) are invaluable tools for investigating enzymatic activity but can suffer from onerous syntheses and low stability in complex proteomes. Herein, we present the first synthesis of a robust, vinyl methyl ester (VME), bearing amino acid, which is compatible with solid phase peptide synthesis (SPPS). Novel peptidic probes incorporating the VME motif were prepared, and their labeling activity was investigated against the deubiquitinating enzyme (DUB) Otubain 1 (OTUB1), a critical cysteine protease DUB with remarkable specificity for Lys48 linked polyubiquitin chains. OTUB1 is implicated in DNA repair and immune response mechanisms and is currently considered a biomarker for tumorigenesis. A probe featuring the VME warhead demonstrated high reactivity and selectivity toward OTUB1, highlighting the significant potential of this approach to create robust and selective covalent tools for interrogating cysteine isopeptidases.

Due to its efficiency, selectivity and biocompatibility, the thiol–ene coupling has demonstrated its potential for protein labelling. Here, we report the electrochemical thiol–ene activation to captur...

Funding opportunities in Chemical Biology, Trinity College Dublin.

Our community recognising scientific excellence.

SNM1A is an enzyme involved in several important biological pathways. To date, most investigations have focused on its role in repairing interstrand c…

The thiol-ene coupling between an alkene and a thiol can be exploited for selective labelling of cysteine residues in protein profiling applications, however, the labelling of complex cell lysate mixt...