NMR assisted design of high affinity ligands for structurally uncharacterized proteins

摘要

Methods of using NMR spectroscopy for identifying ligands that bind to structurally uncharacterized proteins, and improving the binding affinity of ligands for biological targets are disclosed. One aspect of the method includes preparing first NMR spectra of a first complex comprising the biological target and a paramagnetically labeled derivative of a first ligand, preparing a second NMR spectra of a second complex comprising the biological target and a second ligand, and analyzing the spectra to determine whether the second ligand binds to the biological target within the paramagnetic zone of the paramagnetically labeled derivative. The first and second steps may be performed simultaneously, consecutively, or in any order.