Towards a Prediction of Protein Reactivity against Electrophile Ligands 1. Ranking Amino Acid Side Chain Nucleophilicities

摘要

Nucleophilic reactions between electrophilic compounds and proteins are of great interest to characterize covalent protein-ligand interactions. Applications range from anticipating the likelihood of in vivo protein adduction to the mapping of drug binding sites. Electrophiles react with proteins via their nucleophilic amino acids and/or N-terminal amine. To date, there is no general tool to assess the potential for a given electrophilic compound to react with amino acids in a protein. We aim to build a predictive tool to anticipate the reactivity of an electrophilic ligand of interest against a protein target. In the present work, we start with the determination of a scale of nucleophilicity of amino acid side chains against a standard electrophile.