Chemical ligation approaches have become essential tools for theengineering of complex molecules including proteins, nucleic acids andnanoparticles. What makes these reactions so useful is their compatibilitywith the biological 'solvent' water, and a high level of chemoselectivitythat enables their application in complex molecular environments. We haveworked to develop several ligation chemistries that are highlychemoselective and have sufficient ligation rates to be useful at low concentrations. In one case, the use of hydrolysis resistant thioesterpeptides that undergo inter- and intramolecular acyl transfer enables thetotal synthesis of proteins. The optimization of the ligation methodology,improved routes to the required peptide intermediates, and application ofthese methods to complex targets will be presented. Another challenge isthe covalent assembly of macromolecules and nanoparticles. In thesesystems, a 'native' linkage is irrelevant and the main criteria for asuccessful ligation methodology are fast reaction rates and highchemoselectivity. We have found that aniline catalyzed hydrazone and oximereactions enable the controlled assembly and disassembly of macromolecularcomplexes in aqueous solution at micromolar concentrations. The scope ofthese reactions and new approaches for their catalysis will be discussed.

Chemoselective strategies for the synthesis of proteins and labeling of nanoparticles

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.