Development of a biocompatible [3 + 2] azide-alkyne cycloaddition

ORGN 939

Jeremy M. Baskin, baskin@berkeley.edu1, Nicholas J. Agard, nagard@berkeley.edu1, Jennifer A. Prescher, prescher@uclink.berkeley.edu1, Padma R. Gunda, pgunda@berkeley.edu2, and Carolyn R. Bertozzi, crb@berkeley.edu3. (1) Department of Chemistry, University of California, Berkeley, B84 Hildebrand Hall, #1460, Bertozzi Group, Berkeley, CA 94720-1460, (2) Department of Molecular and Cell Biology, University of California, Berkeley, B84 Hildebrand Hall, #1460, Bertozzi Group, Berkeley, CA 94720-1460, (3) Departments of Chemistry and Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720-1460
There is a great need for tools that enable the labeling of biomolecules in vivo. Many site-specific and metabolic methods result in the installation into these macromolecules of the azide, which is inert to biological functionality. In order to detect these azide-labeled biomolecules, the azide must be chemically elaborated using appropriately functionalized secondary reagents. Existing chemistries to modify the azide in this context are limited to the Staudinger ligation and a copper-free variant of “click” chemistry termed the strain-promoted cycloaddition. This promising new ligation, which utilizes ring strain as opposed to cytotoxic copper as a means for alkyne activation, combines the best aspects of the Staudinger ligation and click chemistry: the former's biocompatibility and the latter's sensitivity. Here, we report that the addition of fluorine atoms adjacent to the alkyne results in dramatic rate increases. We are currently exploring the use of these reagents in living animals.

 

Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
1:00 PM-5:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 131, Oral

Division of Organic Chemistry

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