Poster Presentation RACI Biomolecular Division Conference 2013

An expedient and robust synthesis of solid-supported chemical biology probes (#74)

Andrew J.S. Lin 1 , Fiona M Deane 1 , Adam McCluskey 1 , Phillip J. Robinson 2
  1. Chemistry, Centre for Chemical Biology, School of Environmental & Life Science, The University of Newcastle, Callaghan, NSW, Australia
  2. Cell Signaling Unit, Children’s Medical Research Institute, Westmead, NSW, Australia

Chemical biology probes continue to serve as vital tools in drug discovery, providing an insight into the mechanism of biological processes that potentially streamlines lead discovery.

Currently our laboratory has several active drug/lead development programs targeting kinases, GTPases and phosphatases. This inhibitor diversity requires robust approaches for the rapid assembly of chemical biology probes, as shown below (Scheme 1).

The assembly of our Dynaclicks™ employs a facile copper-catalysed Click reaction to assemble, in a LEGO-like building block approach, a wide range of linkers, modified solid supports and potential probes.

621-abstract.jpgScheme 1. Preparation of chemical biology probes 

Herein, we describe our robust and expedient assembly these probes with a range of promiscuous inhibitors that targets a large number protein kinases and dynamin. This presentation will also highlight some of the pull-down findings that result from varying the linker length and the types of solid supports used.