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Natural Product Pre-fractionation

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 May 2008) | Viewed by 21682

Special Issue Editor

Molecular Targets Laboratory, Bldg 560-1, Room 11-86, Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA
Interests: natural products; cancer; HIV; plants; molecular targets

Special Issue Information

Dear Colleagues,

Natural products provide an unparalleled source of chemical diversity for discovery of important and interesting biologically active molecules. This bounty comes at a price, since crude extracts of natural products can be difficult to screen in bioassays, and must be fractionated with guidance from the bioassay to obtain pure compounds. If the active compounds are present in trace amounts this can become a very difficult and time-consuming process, or the activity may be missed altogether. Numerous companies and academic groups have therefore sought to remedy these problems by chromatographically separating the extract to various degrees of resolution. This issue will examine a spectrum of different approaches and provide details on the technical challenges involved, the costs, and the rewards in improved identification of novel natural products.

Dr. John A. Beutler
Guest Editor

Leading papers

  1. Eldridge, G. R.; Vervoort, H. C.; Lee, C. M.; Cremin, P. A.; Williams, C. T.; Hart, S. M.; Goering, M. G.; O'Neil-Johnson, M.; Zeng, L. High-throughput method for the production and analysis of large natural product libraries for drug discovery. Anal.Chem. 2002, 74 (16), 3963-3971.
  2. Bindseil, K. U.; Jakupovic, J.; Wolf, D.; Lavayre, J.; Leboul, J.; van der Pyl, D. Pure compound libraries; a new perspective for natural product based drug discovery. Drug Discov. Today 2001, 6 (16), 840-847.

Published Papers (2 papers)

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487 KiB  
Article
Pre-fractionated Microbial Samples – The Second Generation Natural Products Library at Wyeth
by Melissa M. Wagenaar
Molecules 2008, 13(6), 1406-1426; https://doi.org/10.3390/molecules13061406 - 20 Jun 2008
Cited by 51 | Viewed by 10545
Abstract
From the beginning of the antibiotic era in the 1940s to the present, Wyeth has sustained an active research program in the area of natural products discovery. This program has continually evolved through the years in order to best align with the “current” [...] Read more.
From the beginning of the antibiotic era in the 1940s to the present, Wyeth has sustained an active research program in the area of natural products discovery. This program has continually evolved through the years in order to best align with the “current” drug discovery paradigm in the pharmaceutical industry. The introduction of highthroughput screening and the miniaturization of assays have created a need to optimize natural product samples to better suit these new technologies. Furthermore, natural product programs are faced with an ever shortening time period from hit detection to lead characterization. To address these issues, Wyeth has created a pre-fractionated natural products library using reversed-phase HPLC to complement their existing library of crude extracts. The details of the pre-fractionated library and a cost-benefit analysis will be presented in this review. Full article
(This article belongs to the Special Issue Natural Product Pre-fractionation)
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283 KiB  
Article
Fractionated Marine Invertebrate Extract Libraries for Drug Discovery
by Tim S. Bugni, Mary Kay Harper, Malcolm W.B. McCulloch, Jason Reppart and Chris M. Ireland
Molecules 2008, 13(6), 1372-1383; https://doi.org/10.3390/molecules13061372 - 19 Jun 2008
Cited by 47 | Viewed by 10321
Abstract
The high-throughput screening and drug discovery paradigm has necessitated a change in preparation of natural product samples for screening programs. In an attempt to improve the quality of marine natural products samples for screening, several fractionation strategies were investigated. The final method used [...] Read more.
The high-throughput screening and drug discovery paradigm has necessitated a change in preparation of natural product samples for screening programs. In an attempt to improve the quality of marine natural products samples for screening, several fractionation strategies were investigated. The final method used HP20SS as a solid support to effectively desalt extracts and fractionate the organic components. Additionally, methods to integrate an automated LCMS fractionation approach to shorten discovery time lines have been implemented. Full article
(This article belongs to the Special Issue Natural Product Pre-fractionation)
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