00000nam 2200000zi 4500 9.879168 CaOODSP 20240220151453 m o d f cr cn||||||||| 190911t20082008abca obs f000 0 eng d CaOODSP eng rda CaOODSP eng eng fre D68-6/252-2008E-PDF Chan, Nora W. C., author. High throughput screening of pharmacologically active compounds against botulinum neurotoxin serotype A light chain / Nora W.C. Chan, William E. Lee, DRDC Suffield ; Jessica Wong, Melissa Crichton, David C.W. Mah, Canada West Biosciences Inc. Medicine Hat, Alberta : Defence R&D Canada - Suffield, 2008. ©2008 1 online resource (vii, 14 pages, 2 unnumbered pages) : illustrations (some colour). text txt rdacontent computer c rdamedia online resource cr rdacarrier Technical memorandum ; DRDC Suffield TM 2008-252 "November 2008." Includes bibliographical references (pages 11-12). "Botulinum neurotoxin (BoNT) is the most toxic natural substance known and has long been considered a potential warfare agent. More recently, it has also been considered a growing bioterrorism threat. Unfortunately, there is no effective cure for poisoning, regardless of whether this is a result of deliberate exposure or accidental ingestion of naturally contaminated foodstuffs. Effective countermeasures against BoNT might be achieved by identifying small molecule inhibitors against the toxin's enzymatic active site. To this end, a high throughput screening (HTS) assay based on fluorescence resonance energy transfer (FRET) was established to interrogate small molecule compounds from two proprietary sets of chemical libraries against BoNT serotype A light chain (BoNT/A LC). The chemical libraries were LOPAC (the Library of Pharmaceutically Active Compounds) and the Prestwick Chemical Library (a collection of off- patent drugs). FRET assay buffer conditions were optimized for fast substrate turnover in short incubation time and low background noise. Chemical compound endogenous fluorescence and absorption at 321 nm were measured to address possible interferences. Potential inhibitors and activators of BoNT/A LC were compiled for further comprehensive studies in computational molecular modeling, dose response and enzyme kinetics. Using this HTS method, some 2400 compounds were screened in less than 4 months with minimal instrumentation requirement"--Abstract, page i. Includes abstracts and summaries in English and French. gccst Toxic substances Lee, William Edward, author. Wong, Jessica, author. Crichton, Melissa, author. Mah, David C. W. (David Chow Wah), 1959- author. Defence R&D Canada. Defence R&D Canada - Suffield. Technical memorandum (Defence R&D Canada) DRDC Suffield TM 2008-252. (CaOODSP)9.820564 PDF 681 KB https://publications.gc.ca/collections/collection_2019/rddc-drdc/D68-6-252-2008-eng.pdf