The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors

• Published in: Molecules (Basel, Switzerland) Vol. 18; no. 6; pp. 6408 - 6424
• Main Authors: Santos, Radleigh G, Appel, Jon R, Giulianotti, Marc A, Edwards, Bruce S, Sklar, Larry A, Houghten, Richard A, Pinilla, Clemencia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-05-2013; MDPI
• Subjects: combinatorial libraries; Electronic mail systems; formylpeptide receptors; harmonic mean mixture model; High-Throughput Screening Assays - methods; Inhibitory Concentration 50; Libraries; Ligands; mathematical modeling; mixture-based libraries; Models, Theoretical; Peptide Library; Peptides - chemistry; Peptides - pharmacology; Ratings & rankings; Receptors, Formyl Peptide - antagonists & inhibitors; United States > US
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules18066408

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.