DRA Lectures: NMR-Based strategies for enhancing lead generation

Wednesday, February 22rd, 2006 at 13:15-16:15 in Benzon Auditorium

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

Part 1. Basis for NMR detection of ligand binding

Part 2. Recent NMR experiments for NMR-based screening

Part 3. Applications and outlook of NMR-based screening in drug discovery

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 these 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 remarks about future challenges facing NMR-based screening in the context of drug discovery.

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