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.
Tu
Ying
Y
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Jeffries
Cynthia
C
Ruan
Hong
H
Nelson
Cynthia
C
Smithson
David
D
Shelat
Anang A
AA
Brown
Kristin M
KM
Li
Xing-Cong
XC
Hester
John P
JP
Smillie
Troy
T
Khan
Ikhlas A
IA
Walker
Larry
L
Guy
Kip
K
Yan
Bing
B
D001688:Biological Products; D020650:Combinatorial Chemistry Techniques; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*
D001688:Biological Products