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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Design of proteins using rigid organic macrocycles as scaffolds
1Department of Chemistry, University of British Columbia, Vancouver, Canada.
Abstract:
We have designed and synthesized new three-helix template-assembled synthetic proteins (TASPs) 1a-c. The template was the rigid cyclotribenzylene (CTB) macrocycle 2, which has C3 symmetry. Thiol moieties on the CTB template were used to link cysteine-containing peptide strands 3a-c via disulfide bonds. With designed peptide strands of 15 and 18 residues in length, the structure of TASPs 1a-c were determined to be helical in water according to circular dichroism (CD) spectroscopy. The helicities of TASPs 1a-c were unchanged over large ranges of pH (2-12) and salt concentrations (0-2 M KCl). TASPs 1a-c were also extremely resistant to chemical denaturants: it requires a guanidine hydrochloride (GnHCl) concentration of 7.4 M for TASPs 1a-c to lose 50% of their helicity. The major force for stabilization of TASPs 1a-c is the hydrophobic bundling of the helices.
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