National Cancer Institute (NCI) Program for Natural Products Discovery: Rapid Isolation and Identification of Biologically Active Natural Products from the NCI Prefractionated Library
| Autor: | Barry R. O'Keefe, Curtis J. Henrich, Tanja Grkovic, Matthew J. Harris, Unwoo Kang, John R. Britt, Rhone K. Akee, Kirk R. Gustafson, Jason R. Evans, Susan M. Ensel, Christopher C. Thornburg, Joel P. Schneider, Spencer K. Trinh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Gastropoda Antineoplastic Agents Computational biology 01 natural sciences Biochemistry Proof of Concept Study Mass Spectrometry Small Molecule Libraries 03 medical and health sciences Cell Line Tumor Drug Discovery Spectroscopy Fourier Transform Infrared Animals Humans Hplc method Chromatography High Pressure Liquid Biological Products Haliclona 010405 organic chemistry Extramural Chemistry Drug discovery Active principle Biological activity General Medicine Articles Isolation (microbiology) National Cancer Institute (U.S.) United States 0104 chemical sciences High-Throughput Screening Assays 030104 developmental biology Molecular Medicine Identification (biology) |
| Zdroj: | ACS Chemical Biology |
| ISSN: | 1554-8937 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|