Department of Chemistry



Seth Horne

Associate Professor


1405 Chevron
Chevron Science Center
219 Parkman Avenue

Pittsburgh, PA 15260

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Research Overview

Organic synthesis, bioorganic chemistry, biophysics, protein engineering

Research in the Horne lab is focused on the bioorganic chemistry of proteins. We apply peptides, proteins, and their unnatural analogues as (1) systems to study folding behavior and how to control it, (2) scaffolds for the development of therapeutics, and (3) bio-inspired materials. This interdisciplinary research program spans organic chemistry, biochemistry, biophysics, structural biology, and materials science.

From twenty amino acid building blocks and a simple condensation reaction, Nature produces proteins 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 our imagination and the synthetic ingenuity we apply in the implementation of our ideas. Synthetically modified peptides and proteins can teach us 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 controlling folded conformation. We are working to develop new methods to control peptide folding and create new protein-like objects with defined structure from short oligomers.

The design of molecular species that predictably arrange functional groups in space with sub-nm resolution over 100-1000 nm scales is a difficult problem. Nature is filled with examples of functional supramolecular assemblies, such as the multi-protein complex 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 photosynthetic energy transduction.

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 folds by analogues with unnatural backbones that are resistant to enzymatic degradation.


  • University of Pittsburgh Chancellor's Distinguished Research Award, 2016
  • Thieme Chemistry Journal Award, 2014
  • National Science Foundation CAREER Award, 2012-2017
  • National Institutes of Health Postdoctoral Fellowship, 2006
  • National Science Foundation Graduate Research Fellowship, 2001
  • Goldwater Scholar, 1999


“Heterogeneous-backbone foldamer mimics of zinc finger tertiary structure,” K.L. George, W.S. Horne , J. Am. Chem. Soc., 2017, Pages 7931-7938
“Supramolecular metal-coordination polymers, nets, and frameworks from synthetic coiled-coil peptides,” N.A. Tavenor, M.J. Murnin, W.S. Horne , J. Am. Chem. Soc., 2017, Pages 2212-2215
“Peptide-functionalized semiconductor surfaces: Strong surface electronic effects from minor alterations to backbone composition,” M. Matmor, G.A. Lengyel, W.S. Horne, N. Ashkenasy , Phys. Chem. Chem. Phys., 2017, Pages 5709-5714
“The effects of thioamide backbone substitution on protein stability: A study in α-helical, β-sheet, and polyproline II helical contexts,” C.R. Walters, D.M. Szantai-Kis, Y. Zhang, Z.E. Reinert, W.S. Horne, D.M. Chenoweth, E.J. Petersson , Chem. Sci., 2017, Pages 2868-2877
“Backbone engineering within a latent β-hairpin structure to design inhibitors of polyglutamine amyloid formation,” K. Kar, M.A. Baker, G.A. Lengyel, C.L. Hoop, R. Kodali, I.-J. Byeon, W.S. Horne, P.C.A. van der Wel, R. Wetzel , J. Mol. Biol., 2017, Pages 308-323
“Thermodynamic and structural impact of α,α-dialkylated residue incorporation in a β-hairpin peptide,” M.A. Karnes, S.L. Schettler, H.M. Werner, A.F. Kurz, W.S. Horne, G.A. Lengyel , Org. Lett., 2016, Pages 3902-3905
“Thermodynamic origin of α-helix stabilization by side-chain cross-links in a small protein,” C.M. Haney, H.M. Werner, J.J. McKay, W.S. Horne , Org. Biomol. Chem., 2016, Pages 5768-5773
“Rotameric preferences of a protein spin label at edge-strand β-sheet sites,” T.F. Cunningham, S. Pornsuwan, W.S. Horne, S. Saxena , Prot. Sci., 2016, Pages 1049-1060
“Comparison of design strategies for α-helix backbone modification in a protein tertiary fold,” N.A. Tavenor, Z.E. Reinert, G.A. Lengyel, B.D. Griffith, W.S. Horne , Chem. Commun., 2016, Pages 3789-3792
“Foldamers: Biomimetic and built to order,” W.S. Horne , Nature Chem., 2015, Pages 858-859
“Folding and function in α/β-peptides: Targets and therapeutic applications,” H.M. Werner, W.S. Horne , Curr. Opin. Chem. Biol., 2015, Pages 75-82
“The double histidine Cu2+-binding motif: A highly rigid, site-specific spin probe for electron spin resonance distance measurements,” T.F. Cunningham, M.R. Putterman, A. Desai, W.S. Horne, S. Saxena , Angew. Chem. Int. Ed., 2015, Pages 6330-6334
“Receptor-templated stapling of intrinsically disordered peptide ligands,” C.M. Haney, W.S. Horne , Org. Biomol. Chem., 2015, Pages 4183-4189