Marked small molecule libraries: A new approach to molecular probe design

ORGN 899

Alison N. Hulme, Alison.Hulme@ed.ac.uk1, Iain A. Inverarity, I.A.Inverarity@sms.ed.ac.uk1, and Philip Cohen, p.cohen@dundee.ac.uk2. (1) School of Chemistry, University of Edinburgh, Edinburgh, EH9 3JJ, United Kingdom, (2) School of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom
A truncated approach to the design of molecular probes from small molecule libraries is outlined, based upon the incorporation of a bioorthogonal marker on the molecular scaffold. This has been demonstrated through the synthesis of a focused compound library centered upon the known stress activated protein kinase (SAPK) pathway activator, anisomycin. The active marked library members have been used to synthesize a series of molecular probes, using the copper(I)-catalysed Huisgen cycloaddition reaction. Using this strategy, library members and tags have been coupled in a rapid and atom economical fashion. A series of functionally active molecular probes have been synthesized, containing biotin and fluorophore tags, and these are currently being used to elucidate anisomycin's activation of the SAPK pathways.

 

Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006