Many proteins show potential as therapeutics but are limited in clinical utility by poor stability in serum due to degradation by proteolytic enzymes. For most proteins, biological function is a direct consequence of three-dimensional folded conformation, which is encoded, in turn, by primary amino acid sequence. Unnatural-backbone oligomers with discrete folding behavior (often termed �foldamers�) offer the possibility of combining protein-like biological activity with protease-resistance. Significant advances have been made in recent years related to the design of unnatural oligomers that form helical secondary structures or helix-bundle assemblies; however, more complex tertiary folding remains an elusive target. This talk will describe efforts to develop a set of general rules for the design of protease-resistant analogues of natural proteins that retain the essential tertiary folding behavior of the prototype.

Sequence-based methods for the design of unnatural backbones that manifest the tertiary folding patterns of natural proteins

244th National Meeting (2012)

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