Loading...
Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors
Cruz, Patricia G. Auld, Douglas S. Schultz, Pamela Lovell, Scott Battaile, Kevin P. MacArthur, Ryan Shen, Min Tamayo-Castillo, Giselle Inglese, James Sherman, David H.
Cruz, Patricia G.
Auld, Douglas S.
Schultz, Pamela
Lovell, Scott
Battaile, Kevin P.
MacArthur, Ryan
Shen, Min
Tamayo-Castillo, Giselle
Inglese, James
Sherman, David H.
Citations
Altmetric:
Abstract
The chemical diversity of nature has tremendous potential for discovery of new molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, macro- and microorganisms has curtailed their use in lead discovery efforts. Here we describe a process for leveraging the concentration-response curves (CRCs) obtained from quantitative HTS to improve the initial selection of “actives” from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm aims to improve the probability that labor-intensive subsequent steps of re-culturing, extraction and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by x-ray crystallography.
Description
Date
2012-11-23
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
Citation
Cruz, Patricia G., Douglas S. Auld, Pamela J. Schultz, Scott Lovell, Kevin P. Battaile, Ryan Macarthur, Min Shen, Giselle Tamayo-Castillo, James Inglese, and David H. Sherman. "Titration-Based Screening for Evaluation of Natural Product Extracts: Identification of an Aspulvinone Family of Luciferase Inhibitors." Chemistry & Biology 18.11 (2011): 1442-452.