Current Organic Chemistpy.2006.VoL 10.No.8911 OH D34078 most MS-hased orial libraries 1841 but nun ds to a target and r the sed for ring lig kinetic and ontaining the com ane whic Pulsed Mass Spectrometry pass thre ugh.Once the unb ind material has been washed M5-ly by addition ofNatural Products in Drug Discovery - Concepts Current Organic Chemistry, 2006, Vol. 10, No.8 911 for drug discovery [83]. Basically, most MS-based methods expose a mixture of potential ligands to a target and use MS to detect binders and non-binding molecules by comparing their elution profiles from the compartment in which a target is immobilized or otherwise confined. Alternatively, pure spectroscopic methods directly detect ligand-macromolecule ions in the gas phase. A selection of the most promising procedures which have been recently implemented in drug discovery are presented below. Pulsed Ultrafiltration Mass Spectrometry Pulsed ultrafiltration mass spectrometry is a versatile MS-based approach originally developed by the group of van Breemen at the University of Illinois at Chicago. The method was initially established for the deconvolution of combinatorial libraries [84], but numerous applications have since demonstrated its potential for the screening of natural product extracts as well. Pulsed ultrafiltration MS can also be used for measuring ligand-receptor kinetic and thermodynamic binding parameters. Basically, a pulse containing the compounds to be analysed is injected into a flow-through chamber containing a macromolecular receptor. The chamber is equiped with an ultrafiltration membrane which retains macromolecules and receptor￾ligand complexes but allows low molecular compounds to pass through. Once the unbound material has been washed away with water, the protein-ligand complexes are disrupted by addition of an organic modifier to the mobile phase or by a change in pH. Eluted compounds can be directly analysed by MS or, alternatively, trapped on an HPLC column to HN O OH HO OH O O2N O O OH O OH O OH HO O OH OH O O OH OH OH HO OH OH HO HO OH O O O O OH OH OH O HO HO HO O O OH HO O O O O OH OH OH O O O O O O OH OH OH HO OH OH HO HO OH O O O O O O OH OH HO O OH H O O O O O OH OH OH HO OH OH HO HO OH O O O O O O OH O OH O HO O RD 3-4078 (31) e lla gic a cid (32) corilagi n (33) 36 ge ra niin (34) phyl lanthusi n U (35)