Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability. Here we report our efforts to design and discover a new series of tunable amine-reactive electrophiles (TAREs) for selective and robust labeling of lysine. The major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability. Our work circumvents these challenges by a unique design of the TAREs that form stable adducts with lysine and on reaction with cysteine generate another reactive electrophiles for lysine. We highlight that TAREs exhibit substantially high hydrolytic stability as compared to the activated esters and a...
There is growing interest in reversible and irreversible covalent inhibitors that target noncatalyti...
Targeted covalent inhibitor design is gaining increasing interest and acceptance. A typical covalent...
Protein bioconjugation is an essential tool for the deeper understanding of protein behavior and loc...
Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited a...
Covalent inhibitors have numerous applications as drugs, as tools for drug discovery, and as probes ...
Proteomic profiling using bioorthogonal chemical probes that selectively react with certain amino ac...
Targeted Covalent Inhibitors (TCIs) represent an increasingly important strategy in modern drug disc...
Targeted Covalent Inhibitors (TCIs) represent an increasingly important strategy in modern drug disc...
The covalent inhibition mechanism of action, which overcomes competition with high-affinity, high-ab...
There is a resurging interest in compounds that engage their target through covalent interactions. C...
Cysteines, as one of the most intrinsically nucleophilic amino acids, play important roles in protei...
The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles...
Protein-reactive electrophiles are critical to chemical proteomic applications including activity-ba...
Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug ...
Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug ...
There is growing interest in reversible and irreversible covalent inhibitors that target noncatalyti...
Targeted covalent inhibitor design is gaining increasing interest and acceptance. A typical covalent...
Protein bioconjugation is an essential tool for the deeper understanding of protein behavior and loc...
Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited a...
Covalent inhibitors have numerous applications as drugs, as tools for drug discovery, and as probes ...
Proteomic profiling using bioorthogonal chemical probes that selectively react with certain amino ac...
Targeted Covalent Inhibitors (TCIs) represent an increasingly important strategy in modern drug disc...
Targeted Covalent Inhibitors (TCIs) represent an increasingly important strategy in modern drug disc...
The covalent inhibition mechanism of action, which overcomes competition with high-affinity, high-ab...
There is a resurging interest in compounds that engage their target through covalent interactions. C...
Cysteines, as one of the most intrinsically nucleophilic amino acids, play important roles in protei...
The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles...
Protein-reactive electrophiles are critical to chemical proteomic applications including activity-ba...
Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug ...
Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug ...
There is growing interest in reversible and irreversible covalent inhibitors that target noncatalyti...
Targeted covalent inhibitor design is gaining increasing interest and acceptance. A typical covalent...
Protein bioconjugation is an essential tool for the deeper understanding of protein behavior and loc...