Over the past four decades, we have been studying the chemistry of defense and communication among terrestrial insects and other arthropods, a group of organisms that includes over half of all described species on earth. While many of the compounds we have characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and polypeptides with novel structures which we have discovered in the course of this research. We plan to select approximately ten of the most interesting structures and to prepare pilot-scale libraries consisting of the natural product itself plus -5-30 related structures in quantities suitable for high throughput screening. This project is the culmination, from the viewpoint of drug discovery, of our many years of research in the field of natural products chemistry. ds and proposed derivatives generally represent molecular structures that have not yet been examined via high throughput screening. The likelihood of discovering activities within these libraries of relevance to areas such as neuron-pharmacology, infectious and parasitic diseases, or cancer is much greater than would be expected from a study of other areas of chemical space which are not based on small molecules of biological origin.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM079571-04
Application #
7678358
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (PL))
Program Officer
Schwab, John M
Project Start
2007-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2011-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$270,489
Indirect Cost
Name
Boyce Thompson Institute for Plant Research
Department
Type
DUNS #
045666088
City
Ithaca
State
NY
Country
United States
Zip Code
14853
O'Doherty, Inish; Yim, Joshua J; Schmelz, Eric A et al. (2011) Synthesis of caeliferins, elicitors of plant immune responses: accessing lipophilic natural products via cross metathesis. Org Lett 13:5900-3
Deyrup, Stephen T; Eckman, Laura E; McCarthy, Patrick H et al. (2011) 2D NMR-spectroscopic screening reveals polyketides in ladybugs. Proc Natl Acad Sci U S A 108:9753-8
Chavez, Kathryn J; Feng, Xiaohong; Flanders, James A et al. (2011) Spirocyclic lignans from Guaiacum (Zygophyllaceae) induce apoptosis in human breast cancer cell lines. J Nat Prod 74:1293-7
Forseth, Ry R; Schroeder, Frank C (2011) NMR-spectroscopic analysis of mixtures: from structure to function. Curr Opin Chem Biol 15:38-47
Forseth, Ry R; Fox, Ellen M; Chung, DaWoon et al. (2011) Identification of cryptic products of the gliotoxin gene cluster using NMR-based comparative metabolomics and a model for gliotoxin biosynthesis. J Am Chem Soc 133:9678-81
Mukerjee, Purba; Abid, Mohammed; Schroeder, Frank C (2010) Highly ?-selective hydrolysis of ?,?-epoxyalcohols using tetrabutylammonium fluoride. Org Lett 12:3986-9
Pungaliya, Chirag; Srinivasan, Jagan; Fox, Bennett W et al. (2009) A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:7708-13
Schroeder, Frank C; Taggi, Andrew E; Gronquist, Matthew et al. (2008) NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species. Proc Natl Acad Sci U S A 105:14283-7
Srinivasan, Jagan; Kaplan, Fatma; Ajredini, Ramadan et al. (2008) A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature 454:1115-8