title: Novel affinity ligands for chromatography using combinatorial chemistry.
abstract: Spatially addressable combinatorial libraries were synthesized by solution phase chemistry and screened for binding to human serum albumin. Members of arylidene diamide libraries were among the best hits found, having submicromolar binding affinities. The results were analyzed by the frequency with which particular substituents appeared among the most potent compounds. After immobilization of the ligands either through the oxazolone or the amine substituent, characterization by surface plasmon resonance showed that ibuprofen affected the binding kinetics, but phenylbutazone did not. It is therefore likely that these compounds bind to Site 2 in sub domain IIIA of human serum albumin (HSA).
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tor
authors.initials: T
authors.lastname: Regberg
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lindquist
authors.forename: Ake
authors.initials: A
authors.lastname: Pilotti
authors.forename: Christel
authors.initials: C
authors.lastname: Ellström
authors.forename: Lars
authors.initials: L
authors.lastname: Fägerstam
authors.forename: Ann
authors.initials: A
authors.lastname: Eckersten
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Steven L
authors.initials: SL
authors.lastname: Gallion
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Hogan
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002846:Chromatography, Affinity / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D003432:Cross-Linking Reagents; D057166:High-Throughput Screening Assays; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D010081:Oxazolone / Q000737:chemistry; D010653:Phenylbutazone / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D003432:Cross-Linking Reagents; D008024:Ligands; D012709:Serum Albumin; D010081:Oxazolone; D010653:Phenylbutazone; D007052:Ibuprofen