The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors

Molecules

Radleigh G. Santos³  Jon R. Appel²  Marc A. Giulianotti³  Bruce S. Edwards¹  Larry A. Sklar¹  Richard A. Houghten³ 

[1] Department of Pathology and Center for Molecular Discovery, University of New Mexico, 700 Camino de Salud, Albuquerque, NM 87131, USA; E-Mails:;Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA; E-Mail:;Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA; E-Mails:

关键词: combinatorial libraries;    mixture-based libraries;    harmonic mean mixture model;    mathematical modeling;    formylpeptide receptors;   

DOI  :  10.3390/molecules18066408

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.