Visit ACD/Labs at ASMS
Join us for an hour-long session featuring ACD/Labs staff, collaborators and delicious food. Get the latest on the MS software products featured in our upcoming version ACD/Labs 2012 including a preview of ACD/MS Workbooks—our new advanced interpretation, and knowledge management tools. We'll also discuss advancements in GC/MS data processing, metabolite identification, and impurity characterization. See software demos and learn how ACD/Labs is collaborating with instrument vendors to create innovative and effective new tools for MS analysis.
Location: Vancouver Convention Center
Space for this event is limited so please register in advance.
Title: Dereplication Tools for Natural Products Research: The Highlights
Presenter: Nicholas H. Oberlies, Ph.D. (University of North Carolina at Greensboro)
Abstract: View Abstract
Natural products, in general, and compounds from fungi, specifically, have a long and storied history in the development of medicines. In ongoing studies to explore filamentous fungi for anticancer drug leads, over 100 compounds have been isolated and characterized over the past four years, with approximately 25 to 35 compounds being discovered annually. Over 30% of the isolated leads represent new chemical entities. Of the known compounds, approximately 40% have not been studied previously for anticancer activities, and thus their biological evaluation is germane to the larger goals of the project. Although more than 230,000 compounds have been described from nature, only about 13,000 of these have been from fungi. Thus, our library represents about 1% of the compounds described by fungi.
To expedite the discovery of new leads, and to avoid re-isolation of previously known compounds, a UPLC-PDA-HRMS method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of compounds isolated to date, utilizing both positive and negative ionization modes. Additional information, such as UV-absorption maxima and retention times, were also recorded. Screener cultures and/or fractions that showed cytotoxic activities were dereplicated before engaging in the isolation/purification process. Examples will be presented that demonstrate the speed and efficiencies with these procedures, particularly in conjunction with software programs that help collate the data. In summary, the dereplication methods allow us to focus limited human and financial resources upon those bioactive samples that have the most promise to yield structurally unique leads.