Session: Current Topics in Biological Chemistry:

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a biorthogonal reaction widely used in imaging, labeling, and modifications of proteins. The toxicity of copper requires its removal from the biological samples, which is nontrivial. To avoid this complication Cu–Free Click Chemistry (SPAAC) reaction is frequently used for biological molecules, despite the high hydrophobicity of the incorporated dibenzocyclooctyne derivative. As an alternative approach, we are developing different copper-ligand complexes on a solid support, with which we shall do CuAAC reaction of biological molecules under aqueous conditions. The immobilization of the copper-ligand complexes on solid support will minimize the complication of copper removal from samples, provided the copper leaching from the solid is negligible.
Here we show the solid support synthesis of selected catalysts, stringent wash protocols with copper quantification by UV-Vis, and the cycloaddition performance of the catalysts under different conditions, monitored by HPLC and ESI LC-MS. For the cycloaddition reaction, two model peptides with the sequence 2-azidoacetic acid-GVGA-CONH₂ and 4-Pentynoic acid-GAGA-CONH₂ were synthesized. Our results show that copper leaching is ligand-dependent, solvent-dependent, and time-dependent and can be prevented by removing most of the copper by stringent washes. Schiff’s base ligands showed promising performance on TentaGel resin, so we compare a (diphenylphosphaneyl)benzylidene and a pyrridin-2-ylmethylene Schiff’s base ligand. We shall present the results for our ongoing experiments and the effect of different modifications to the catalyst.

Mr. Rene Kandler

Clark University

Appearances