title: The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.
abstract: In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA. rsantos@tpims.org
authors.forename: Radleigh G
authors.initials: RG
authors.lastname: Santos
authors.forename: Jon R
authors.initials: JR
authors.lastname: Appel
authors.forename: Marc A
authors.initials: MA
authors.lastname: Giulianotti
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Edwards
authors.forename: Larry A
authors.initials: LA
authors.lastname: Sklar
authors.forename: Richard A
authors.initials: RA
authors.lastname: Houghten
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
mesh_terms: D057166:High-Throughput Screening Assays / Q000379:methods*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008962:Models, Theoretical; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors*
chemical_list: D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D044042:Receptors, Formyl Peptide