Details of Grant 

EPSRC Reference:	GR/S99419/01
Title:	Diversity-oriented synthesis and chemical biology of unnatural products
Principal Investigator:	Nelson, Professor AS
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Sch of Chemistry
Organisation:	University of Leeds
Scheme:	Advanced Fellowship (Pre-FEC)
Starts:	01 October 2004	Ends:	30 September 2009	Value (£):	290,726
EPSRC Research Topic Classifications:	Chemical Biology Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 21 Apr 2004 Chemistry Fellowships Interview Panel 2004 Deferred 18 Mar 2004 Chemistry Fellowships Sift Panel 2004 Deferred
Summary on Grant Application Form
It is unlikely that natural products alone will provide all of the chemical tools to study the functions of all proteins. This fellowship will focus on (a) the development of methods for the synthesis of conformationally and structurally diverse unnatural products and (b) the exploitation of these molecules in chemical biology. Two complementary approaches for the synthesis of polyketide-like libraries will be investigated. Unnatural products, including aminoglycoside and indolocarbazole alkaloid derivatives already available in the group,will be used to ablate the molecular interactions of specific macromolecular targets, to discover new potent ligands for biologically important RNAs, to probe bivalent interactions, and to act as tailored phosphodonors for specific protein kinases.The proposal will tackle EPSRC objectives for 2003/4, namely (a) to increase research capability and international competitiveness in a strategic area (chemical biology, as recognised by Whitesides et al), (b) to support interdisciplinary research, new researchers and high-risk research proposalsStructural molecular, cell and chemical biologists in the pharmaceutical and agrochemical industries and in academia:The analysis of macromolecular interactions, and the elucidation of phosphorylation cascades, are major challenges for the decade or more. The solution of such problems will expose new drug targets, and will reveal entirely new strategies for future therapies. Novel protocols will be developed for the routine synthesis of unnatural product libraries (c.f. nucleic acid and peptide libraries). Reagents and catalysts for these syntheses, fluorescent sensors for studying bivalent interations and novel phosphodonor substrates could, in the future be sold to these scientists.Between twenty-five and forty postdoctoral co-workers and PhD students:An estimated 25-40 co-workers will be working within the Nelson group during the period of the five-year fellowship. These workers will contribute to a highly active, interdisciplinary research programme in which complex synthetic chemistry is applied to cutting-edge problems in chemical biology. They will interact with scientists from undergraduate to professorial level and will be involved in weekly group meetings concerning all aspects of organic chemistry and chemical biology. The experience will provide them with an ideal training for employment in academia, the pharmaceutical and agrochemicals industries, the fine chemicals industries and emerging biotechnological industries.Related Proposals: If this application is a resubmission or seeking an extension, please give previous reference number (if known), title and date of submission.
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Organisation Website:	http://www.leeds.ac.uk