Rhenium(V) Complexes as Cysteine-Targeting Coordinate Covalent Warheads.
J Med Chem
; 66(4): 3088-3105, 2023 02 23.
Article
in English
| 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Rhenium
/
Cysteine Proteinase Inhibitors
/
Cysteine
/
Cysteine Proteases
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
J Med Chem
Journal subject:
Chemistry
Year:
2023
Document Type:
Article
Affiliation country:
Acs.jmedchem.2c02074
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