Analytical ultracentrifugation: a powerful ?new? technology in drug discovery - Aggregation & Cleavage

Analytical ultracentrifugation: a powerful ?new? technology in drug discovery
December 2004
Tom Laue
Drug Discovery Today: Technologies
Abstract
Analytical ultracentrifugation (AUC) is a powerful means of characterizing the solution behavior of molecules. Sedimentation velocity analysis, the preferred AUC technique for characterizing complex systems, has higher resolution, broader applicable range and fewer solute/solvent limitations than gel-permeation chromatography. The technique is simple to perform and should become a mainstay for target identification, target validation, lead optimization, formulation in drug development and QA/QC. Recent studies have used AUC to characterize the binding stoichiometry and binding sites of an anti-tumor agent; of a hemoglobin-stabilizing protein, and of a fibril growth inhibitor, and to assess the causes of protein aggregation. The recent addition of fluorescence to the existing absorbance and interference detectors dramatically extends the flexibility of analytical ultracentrifugation.
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