Automated high-throughput system to fractionate plant natural products for drug discovery.
The development of an automated, high-throughput fractionation procedure to prepare and analyze natural product libraries for drug discovery screening is described. Natural products obtained from plant materials worldwide were extracted and first prefractionated on polyamide solid-phase extraction cartridges to remove polyphenols, followed by high-throughput automated fractionation, drying, weighing, and reformatting for screening and storage. The analysis of fractions with UPLC coupled with MS, PDA, and ELSD detectors provides information that facilitates characterization of compounds in active fractions. Screening of a portion of fractions yielded multiple assay-specific hits in several high-throughput cellular screening assays. This procedure modernizes the traditional natural product fractionation paradigm by seamlessly integrating automation, informatics, and multimodal analytical interrogation capabilities.
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Ying
Y
Tu
Cynthia
C
Jeffries
Hong
H
Ruan
Cynthia
C
Nelson
David
D
Smithson
Anang A
AA
Shelat
Kristin M
KM
Brown
Xing-Cong
XC
Li
John P
JP
Hester
Troy
T
Smillie
Ikhlas A
IA
Khan
Larry
L
Walker
Kip
K
Guy
Bing
B
Yan
D001688:Biological Products; D020650:Combinatorial Chemistry Techniques; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*
D001688:Biological Products