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National Cancer Institute (NCI) Program for Natural Products Discovery: Rapid Isolation and Identification of Biologically Active Natural Products from the NCI Prefractionated Library

  1. Author:
    Grkovic,Tanja
    Akee,Rhone
    Thornburg,Chris
    Trinh,Spencer
    Britt,John
    Harris,Matthew
    Evans,Jason
    Kang, Unwoo
    Ensel, Susan
    Henrich,Curtis
    Gustafson,Kirk
    Schneider,Joel
    O'Keefe,Barry

  2. Author Address

    Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nat Prod Support Grp, Frederick, MD 21702 USA.NCI, Ctr Canc Res, Nat Prod Branch, Dev Therapeut Program,Div Canc Treatment, Frederick, MD 21701 USA.NCI, Ctr Canc Res, Diag & Mol Targets Program, Frederick, MD 21701 USA.NCI, Ctr Canc Res, Mol Targets Program, Frederick, MD 21702 USA.Hood Coll, Dept Chem & Phys, Frederick, MD 21701 USA.Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.NCI, Ctr Canc Res, Chem Biol Lab, Frederick, MD 21702 USA.
    1. Year: 2020
    2. Date: Apr 17
  2. Journal: ACS CHEMICAL BIOLOGY
  3. AMER CHEMICAL SOC,
    1. 15
    2. 4
    3. Pages: 1104-1114
  5. Type of Article: Article
  6. ISSN: 1554-8929
  1. Abstract:

    An automated, high-capacity, and high-throughput procedure for the rapid isolation and identification of biologically active natural products from a prefractionated library is presented. The semipreparative HPLC method uses 1 mg of the primary hit fraction and produces 22 subfractions in an assay-ready format. Following screening, all active fractions are analyzed by NMR, LCMS, and FTIR, and the active principle structural classes are elucidated. In the proof-of-concept study, we show the processes involved in generating the subfractions, the throughput of the structural elucidation work, as well as the ability to rapidly isolate and identify new and biologically active natural products. Overall, the rapid second-stage purification conserves extract mass, requires much less chemist time, and introduces knowledge of structure early in the isolation workflow.

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External Sources

  1. View Full Text
  2. DOI: 10.1021/acschembio.0c00139
  3. PMID: 32223208
  4. PMCID: PMC7171602
  5. View record in Web of Science®
  6. WOS: 000526890700036

Library Notes

  1. Fiscal Year: FY2019-2020
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