Organic synthesis, bioorganic chemistry, biophysics, protein engineering

Research in the Horne lab is focused on the design, synthesis, and study of synthetic analogues of polypeptides and proteins. From twenty different amino acid building blocks and a simple condensation reaction, Nature produces proteins, entities that perform the cellular functions underlying life. As chemists, we can modify the covalent structure of proteins and other biomolecules in ways limited only by the creativity of our designs and the synthetic ingenuity we apply in the implementation of our ideas. Synthetically modified peptides and proteins can teach us new things about natural biological processes and also act as scaffolds for the design of molecules that are inspired by nature but manifest new and interesting functions.

Short peptides and peptidomimetics with defined folds can mimic surfaces of natural proteins and block protein-protein interactions involved in disease. A key challenge in design of such species is the development of strategies for controlling folded conformation. We are developing new strategies to control peptide folding and to create new protein-like objects with defined folded structures from short polypeptide oligomers.

The design of large molecular species that can predictably arrange functional groups in space with sub-nm accuracy over 100-1000 nm scales is a difficult problem. Nature is filled with examples of functional supramolecular assemblies, such as photosystem II. We are working to utilize biological recognition motifs in order to generate molecules capable of directed self-assembly to form supramolecular light harvesting chromophore arrays that mimic aspects of photosynthesis.

In a protein, the sequence of amino acid side chains determines folded structure and function. Protein backbones can tolerate a surprising degree of chemical modification without compromising sequence-encoded folding. We are working to develop general strategies for the sequence-based mimicry of protein tertiary structures by analogues with unnatural backbones.