Rhenium(V) Complexes as Cysteine-Targeting Coordinate Covalent Warheads.
J Med Chem
; 66(4): 3088-3105, 2023 02 23.
Artículo
en Inglés
| MEDLINE | ID: covidwho-2265584
ABSTRACT
Interest in covalent enzyme inhibitors as therapeutic agents has seen a recent resurgence. Covalent enzyme inhibitors typically possess an organic functional group that reacts with a key feature of the target enzyme, often a nucleophilic cysteine residue. Herein, the application of small, modular ReV complexes as inorganic cysteine-targeting warheads is described. These metal complexes were found to react with cysteine residues rapidly and selectively. To demonstrate the utility of these ReV complexes, their reactivity with SARS-CoV-2-associated cysteine proteases is presented, including the SARS-CoV-2 main protease and papain-like protease and human enzymes cathepsin B and L. As all of these proteins are cysteine proteases, these enzymes were found to be inhibited by the ReV complexes through the formation of adducts. These findings suggest that these ReV complexes could be used as a new class of warheads for targeting surface accessible cysteine residues in disease-relevant target proteins.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Renio
/
Inhibidores de Cisteína Proteinasa
/
Cisteína
/
Proteasas de Cisteína
/
SARS-CoV-2
/
COVID-19
Límite:
Humanos
Idioma:
Inglés
Revista:
J Med Chem
Asunto de la revista:
Química
Año:
2023
Tipo del documento:
Artículo
País de afiliación:
Acs.jmedchem.2c02074
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