Special Issue on Natural Product Pre-fractionation

John A. Beutler, Ph.D.
Molecular Targets Development Program
Bldg.560-15,
NCI at Frederick
Frederick, MD 21702-1201, USA
(301)846-1942; (301)514-9814 cell; (301)846-6177 fax
E-mail: jb123w@nih.gov
http://home.ncifcrf.gov/mtdp/

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.

Manuscript ID: pre-fractionation-20071015-Wagenaar-us
Title: Pre-fractionated Microbial Samples – The Second Generation Natural Products Library at Wyeth
Author: Melissa M. Wagenaar
E-mail: Wagenam@wyeth.com
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” drug discovery paradigm in the pharmaceutical industry.  The introduction of high throughput 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.

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.

Manuscripts should be prepared according to the Instructions for Authors and submitted by e-mail before 30 May 2008 to molecules@mdpi.org and a copy to jb123w@nih.gov and mcphee@mdpi.org. The subject title of the message should be "Molecules Manuscript for Special Issue on Natural Product Pre-fractionation".

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