Cross-Correlated 19F Relaxation Measurements for the Study of Fluorinated Ligand–Receptor Interactions

✍ Scribed by Jeffrey W. Peng

• Publisher: Elsevier Science
• Year: 2001
• Tongue: English
• Weight: 180 KB
• Volume: 153
• Category: Article
• ISSN: 1090-7807
• DOI: 10.1006/jmre.2001.2422

✦ Synopsis

Fluorine is often used in drug-design efforts to enhance the pharmacokinetic properties of biologically active compounds. Additionally fluorine nuclei ( 19 F) have properties that are well suited to current pharmaceutical NMR screening programs. Together, these considerations have motivated our interest in the utility of fluorine relaxation parameters to study ligand-receptor interactions. Here, we investigate the potential for cross-correlated relaxation effects between the 19 F anisotropic chemical-shift and 19 F-1 H dipoledipole relaxation mechanisms to help pinpoint and quantify exchange processes. Methods are proposed and demonstrated in which the magnitude ratio of the transverse cross-correlation rate constant η xy and the fluorine transverse relaxation rate constant, R 2 , help estimate the exchange rate constant for ligand-binding equilibria. These exchange rate constants provide estimates of the ligand dissociation rate constants k off and can thus provide a means for rank-ordering the binding affinities of ligands identified in pharmaceutical screens.