Solid-state NMR spectroscopy as a tool for drug design: from membrane-embedded targets to amyloid fibrils.
Structure-based design has gained credibility as a valuable component of the modern drug discovery process. The technique of SSNMR (solid-state NMR) promises to be a useful counterpart to the conventional experimental techniques of X-ray crystallography and solution-state NMR for providing structural features of drug targets that can guide medicinal chemistry towards drug candidates. This article highlights some recent SSNMR approaches from our group for identifying active compounds, such as enzyme inhibitors, receptor antagonists and peptide agents, that prevent the aggregation of amyloid proteins involved in neurodegenerative diseases. It is anticipated that the use of SSNMR in drug discovery will become more widespread in the wake of advances in hardware and methodological developments.
Middleton
D A
DA
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, U.K. middleda@liv.ac.uk
D000682:Amyloid / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D015195:Drug Design; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed
D000682:Amyloid; D008024:Ligands