Lysine-Targeting Reversible Covalent Inhibitors with Long Residence Time.
J Am Chem Soc
; 144(3): 1152-1157, 2022 01 26.
Article
em En
| MEDLINE
| ID: mdl-35040658
ABSTRACT
We report a new reversible lysine conjugation that features a novel diazaborine product and much slowed dissociation kinetics in comparison to the previously known iminoboronate chemistry. Incorporating the diazaborine-forming warhead RMR1 to a peptide ligand gives potent and long-acting reversible covalent inhibitors of the staphylococcal sortase. The efficacy of sortase inhibition is demonstrated via biochemical and cell-based assays. A comparative study of RMR1 and an iminoboronate-forming warhead highlights the significance and potential of modulating bond dissociation kinetics in achieving long-acting reversible covalent inhibitors.
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MEDLINE
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Lisina
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En
Ano de publicação:
2022
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Article