title: Exploring the active site of human factor Xa protein by NMR screening of small molecule probes.
abstract: A collection of small molecules (MW < 350 Da) was screened for binding to human factor Xa using saturation transfer difference NMR spectroscopy to detect binding. The NMR screening experiments identified four hits. Binding isotherms constructed from NMR linewidth data showed that the binding affinities of the hits were all in the 30-210 microM range. Competition binding experiments showed that three of the ligands were displaced by a known microM inhibitor of factor Xa. The success of the method for identifying new ligands and the relevance of this information to the design of new factor Xa inhibitors are discussed.
authors.affiliation: Department of Analytical Chemistry, Organon Laboratories Ltd, Newhouse, Lanarkshire, UK ML1 5SH. l.fielding@organon.co.uk
authors.forename: Lee
authors.initials: L
authors.lastname: Fielding
authors.forename: Dan
authors.initials: D
authors.lastname: Fletcher
authors.forename: Samantha
authors.initials: S
authors.lastname: Rutherford
authors.forename: Jasmit
authors.initials: J
authors.lastname: Kaur
authors.forename: Jordi
authors.initials: J
authors.lastname: Mestres
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D015951:Factor Xa / Q000737:chemistry* / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D004791:Enzyme Inhibitors; D065427:Factor Xa Inhibitors; D008024:Ligands; D015335:Molecular Probes; D015951:Factor Xa