Analytical Sciences

Abstract − Analytical Sciences, 19(10), 1441 (2003).

Segment Identification of a Ligand Binding with a Protein Receptor Using Multidimensional T1 ρ-, Diffusion-Filtered and Diffusion-Ordered NOESY Experiments
Hiroaki UTSUMI,* Hiroko SEKI,** Kentaro YAMAGUCHI,** and Mitsuru TASHIRO*** 
*NM Application & Research Group, Application & Research Center, Analytical Instruments Division, JEOL Ltd., Musashino, Akishima, Tokyo 196-8558, Japan
**Chemical Analysis Center, Chiba University, Yayoi, Inage, Chiba 263-8522, Japan
***Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Minami-Osawa, Hachioji, Tokyo 192-0367, Japan
Multidimensional T1 ρ-, diffusion-filtered and diffusion-ordered NOESY techniques were applied to identify segments of a ligand binding with a protein receptor. These experiments can easily provide intermolecular NOEs of the complex, which are of great significance for characterizing the binding epitopes of a ligand. This information cannot be obtained by high-throughput 1D NMR experiments, used for determining the binding affinity, although multidimensional NMR experiments require more experiment time. The present results indicate that the current experiments using T1 ρ- and diffusion-edited techniques are very suitable for identifying segments of a ligand binding with a protein receptor in the drug discovery process.