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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Philip Dawson, The Scripps Research Institute
Chemoselective strategies for the synthesis of proteins and labeling of nanoparticles
Chemical ligation approaches have become essential tools for the engineering of complex molecules including proteins, nucleic acids and nanoparticles. What makes these reactions so useful is their compatibility with the biological "solvent" water, and a high level of chemoselectivity that enables their application in complex molecular environments. We have worked to develop several ligation chemistries that are highly chemoselective and have sufficient ligation rates to be useful at low concentrations. In one case, the use of hydrolysis resistant thioester peptides that undergo inter‐ and intramolecular acyl transfer enables the total synthesis of proteins. The optimization of the ligation methodology, improved routes to the required peptide intermediates, and application of these methods to complex targets will be presented. Another challenge is the covalent assembly of macromolecules and nanoparticles. In these systems, a "native" linkage is irrelevant and the main criteria for a successful ligation methodology are fast reaction rates and high chemoselectivity. We have found that aniline catalyzed hydrazone and oxime reactions enable the controlled assembly and disassembly of macromolecular complexes in aqueous solution at micromolar concentrations. The scope of these reactions and new approaches for their catalysis will be discussed.
For more information contact Prof. Andrew Lyon (404-894-4090).
