title: Protein affinity map of chemical space.
abstract: Affinity fingerprinting is a quantitative method for mapping chemical space based on binding preferences of compounds for a reference panel of proteins. An effective reference panel of <20 proteins can be empirically selected which shows differential interaction with nearly all compounds. By using this map to iteratively sample the chemical space, identification of active ligands from a library of 30,000 candidate compounds has been accomplished for a wide spectrum of specific protein targets. In each case, <200 compounds were directly assayed against the target. Further, analysis of the fingerprint database suggests a strategy for effective selection of affinity chromatography ligands and scaffolds for combinatorial chemistry. With such a system, the large numbers of potential therapeutic targets emerging from genome research can be categorized according to ligand binding properties, complementing sequence based classification.
authors.affiliation: Terrapin Technologies, Inc., San Francisco, CA 94080, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Kauvar
authors.forename: H O
authors.initials: HO
authors.lastname: Villar
authors.forename: J R
authors.initials: JR
authors.lastname: Sportsman
authors.forename: D L
authors.initials: DL
authors.lastname: Higgins
authors.forename: D E
authors.initials: DE
authors.lastname: Schmidt
mesh_terms: D002846:Chromatography, Affinity / Q000379:methods*; D003628:Database Management Systems; D005454:Fluorescence Polarization; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012015:Reference Standards
chemical_list: D008024:Ligands; D011506:Proteins