Due to their significant roles in biological processes, proteins have been intensely investigated as sources of novel drugs. Successful therapeutics have been developed from natural protein sequences yet their efficacy is often limited by poor serum stability due to endogenous proteases. One solution is to replace the natural backbone of proteins with unnatural moieties. Significant efforts have been devoted to design mimics of protein secondary structures; however, few examples of tertiary structure mimicry by unnatural backbones have been reported. We describe here the systematic backbone alteration of a natural protein sequence with a well-defined tertiary fold. The result is a series of unnatural oligomers with highly unnatural backbones but folds similar to that of the wild-type sequence. Our results suggest a potentially general strategy for tertiary structure mimicry of other protein sequences.

Protein-like tertiary folding from oligomers with highly unnatural backbones

246th National Meeting (2013)

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