DRA Lectures: I. Basis for NMR detection of ligand binding, II. Recent NMR experiments for NMR-based screening and III. Applications and outlook of NMR-based screening in drug discovery

Wednesday, February 23th, 2005 at 9:15-12:15 in Benzon Auditorium

The Danish University of Pharmaceutical Sciences Universitetsparken 2, 2100 Copenhagen O

University of Notre Dame, Department of Chemistry and Biochemistry, Notre Dame, Indiana, USA

In the past ~7 years, Nuclear Magnetic Resonance (NMR) spectroscopy has become recognized as a tool for accelerating the identification of new chemical lead compounds in drug discovery. This is due mainly to the ability of NMR to screen libraries of compounds for binding to therapeutic macromolecular targets (e.g. proteins), and then further exploiting this binding information to help select or modify leads. The overall goal of this course section is to provide a basic knowledge of the NMR experiments underlying such NMR-based screening, and how they have impacted pharmaceutical research. To this end, this part of the course will discuss three topic areas.

· First, we will discuss of the physical basis underlying NMR's ability to reveal ligand binding. In particular, we will discuss how different NMR spectral parameters vary in their sensitivity to binding.

· Second, we will explain some of the more popular NMR experiments used to detect ligand-binding and their associated experimental protocols. While tese will include both ligand and target-based approaches, we will have a stronger emphasis on the former.

· Finally, we will review some of the actual NMR screening strategies used in recent pharmaceutical research. We will discuss these methods in the context of their impact, and their compatibility with industrial research settings.

We will conclude with some brief remarks about future challenges facing NMR-based screening in the context of drug discovery.

1. C. A. Lepre, J. M. Moore & J. W. Peng "Theory and applications of NMR-based screening in pharmaceutical research" Chem. Rev. 2004, 104, 3641-3675.

2. J. W. Peng, J. Moore & N. Abdul-Manan "NMR experiments for lead generation in drug discovery" Progr. Magn. Res. Spectr. 2004, 44, 225-256.

The lecture is organised by: Jerzy Jaroszewski (the Danish University of Pharmaceutical Sciences) and is open for attendance by all interested parties.