Targeting Histidine for Developing a New Generation of Covalent Enzyme Inhibitors

Title:Targeting Histidine for Developing a New Generation of Covalent Enzyme Inhibitors

Volume: 17 Issue: 3

Author(s): Donald Poirier*

Affiliation:

• Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec Research Center, Québec, QC,Canada

Keywords: Covalent inhibitor, irreversible inhibitor, targeted inhibitor, enzyme, histidine, drug.

Abstract: Despite the significant number of irreversible inhibitors developed over the years, strong prejudices remain for this type of therapeutic molecule, particularly in the area of drug development. New generations of covalent targeted inhibitors are, however, in development, and interest is increasingly growing. In fact, the new generation of covalent inhibitors has a weakly reactive species (warhead) that is able, in a particular context, to selectively form a chemical bond with a given amino acid residue, which can be irreversible or reversible. In addition to new selective warheads, new amino acids are also targeted. In the following text, we will focus on covalent targeted inhibitors that selectively alkylate histidine.

Cite this article as:

Poirier Donald *, Targeting Histidine for Developing a New Generation of Covalent Enzyme Inhibitors, Current Enzyme Inhibition 2021; 17 (3) . https://dx.doi.org/10.2174/1573408017666211008141335