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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.


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.

SUBMITTER: Grkovic T 

PROVIDER: S-EPMC7171602 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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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.

Grkovic Tanja T   Akee Rhone K RK   Thornburg Christopher C CC   Trinh Spencer K SK   Britt John R JR   Harris Matthew J MJ   Evans Jason R JR   Kang Unwoo U   Ensel Susan S   Henrich Curtis J CJ   Gustafson Kirk R KR   Schneider Joel P JP   O'Keefe Barry R BR  

ACS chemical biology 20200407 4


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 proces  ...[more]

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