HNF4α Is a Covalent Bond-Forming Receptor

Abstract

HNF4α is a nuclear receptor whose ligands are fatty acids. HNF4α is a target molecule for drug discovery research and thus we tested its covalent binding ability to investigate the possible development of covalent modifiers of HNF4α. Oxidized polyunsaturated fatty acids (oxo-PUFAs) have moderate flexibility and possess a Michael acceptor that participates in conjugate addition reactions with nucleophilic amino acid residues. Thus, oxo-PUFAs were used as probes and their covalent binding abilities to HNF4α were verified. Several oxo-PUFAs, such as 4-oxoDHA, were shown to be covalent modifiers of HNF4α and therefore we concluded that HNF4α can form covalent bonds to ligands.

Keywords: HNF4α; PUFA; covalent modifire; nuclear receptor; oxo-fatty acid.