title: Screening a fragment cocktail library using ultrafiltration.
abstract: Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar K(d), the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Korotkov
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Delarosa
authors.forename: Alberto
authors.initials: A
authors.lastname: Napuli
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kelley
authors.forename: Natasha
authors.initials: N
authors.lastname: Mueller
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ross
authors.forename: Frank H
authors.initials: FH
authors.lastname: Zucker
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Buckner
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Merritt
authors.forename: Christophe L M J
authors.initials: CL
authors.lastname: Verlinde
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Van Voorhis
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Hol
authors.forename: Erkang
authors.initials: E
authors.lastname: Fan
mesh_terms: D001667:Binding, Competitive; D055808:Drug Discovery / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism; D008024:Ligands; D010967:Plasmodium yoelii / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000378:metabolism; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries