Guintu, Christina, Kwok, Michael, Hanlon, James, Spalding, Tracy, Wolff, Karen, Yin, Hong, Kuhen, Kelli, Sasher, Kimberly, Calvin, Paul, Jiang, Shumei, Zhou, Yingyao and Isbell, John (2006) Just-in-time purification: an effective solution for cherry-picking and purifying active compounds from large legacy libraries. Journal of Biomolecular Screening : the official journal of the Society for Biomolecular Screening, 11 (8). pp. 933-939. ISSN 1087-0571

Abstract

Many companies possess a compound collection consisting of purified compounds and of unpurified products from combinatorial libraries. Using commercial and proprietary compounds as examples, this report provides clear examples of the significant impact purification can have on the activity observed for a compound and highlights the need to retest the purified compounds prior to creating structure-activity relationships. Crude mixtures made with commercial compounds led to an increase in the number of false positives in the SXR-GAL4 assay as compared with their pure and purified counterparts. An examination of proprietary compounds in an HIV assay resulted in the purification of 61 active crude synthetic mixtures. Of these 61 compounds, 32 were 5-fold less active and 2 were 5-fold more active after purification. This report details a semiautomated process developed and implemented for cherry-picking, tracking, and selectively purifying compounds found active in high-throughput screening campaigns.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	purification, false positives, high-throughput screening, purification, SXR, HIV
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 14:04
Last Modified:	31 Jan 2013 01:26
URI:	https://oak.novartis.com/id/eprint/137