DiffErential EPitope mapping by STD NMR spectroscopy (DEEP-STD NMR) to reveal the nature of protein-ligand contacts.
 

DiffErential EPitope mapping by STD NMR spectroscopy (DEEP-STD NMR) to reveal the nature of protein-ligand contacts.

DiffErential EPitope mapping by STD NMR spectroscopy (DEEP-STD NMR) to reveal the nature of protein-ligand contacts.

Angew Chem Int Ed Engl. 2017 Oct 04;:

Authors: Monaco S, Tailford LE, Juge N, Angulo J

Abstract
STD NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Here we report the development of a novel protocol, Differential Epitope Mapping by STD NMR (DEEP-STD NMR), to identify the type of protein residues contacting the ligand. The protocol produces Differential Epitope Maps by performing (1) differential frequencies STD NMR and/or (2) differential solvent (D2O/H2O) STD NMR experiments. Both approaches provide different complementary information on the binding pocket. We demonstrate that DEEP-STD NMR can be used to readily obtain pharmacophore information on the protein. Furthermore, if the 3D structure of the protein is known, this information also helps orienting the ligand in the binding pocket.


PMID: 28977722 [PubMed - as supplied by publisher]



More...