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Synthetic Molecular Evolution of Peptides

Synthetic molecular evolution is an iterative process of designing combinatorial libraries, based on known sequences, and screening the libraries orthogonally for members that have a particular set of desired properties.

We have used synthetic molecular evolution to discover:

  • Pore-forming peptides that have antiviral activity
  • Pore-forming peptides to enable macromolecule delivery
  • Antibacterial peptides that kill drug-resistant pathogens
  • Membrane translocating peptides for delivery
  • Cell-penetrating peptides for delivery
  • Membrane-spanning helical dimers for engineering
     

Recent Publications:

Wiedman G, Kim SY, Zapata-Mercado E, Wimley WC, Hristova K. pH-Triggered, Macromolecule-Sized Poration of Lipid Bilayers by Synthetically Evolved Peptides. J Am Chem Soc. 2017 139(2):937-945. doi PubMed PMC (Collaboration with the Hristova Lab at Johns Hopkins)

Krauson AJ, Hall OM, Fuselier T, Starr CG, Kauffman WB, Wimley WC. Conformational Fine-Tuning of Pore-Forming Peptide Potency and Selectivity. J Am Chem Soc. 2015 Dec 30;137(51):16144-52. doi PubMed PMC

Krauson AJ, He J, Wimley AW, Hoffmann AR, Wimley WC. Synthetic molecular evolution of pore-forming peptides by iterative combinatorial library screening. ACS Chem Biol. 2013, 8(4):823-31. doi PubMed PMC

Krauson AJ, He J, Wimley WC. Gain-of-function analogues of the pore-forming peptide melittin selected by orthogonal high-throughput screening. J Am Chem Soc. 2012 Aug 1;134(30):12732-41. doi PubMed PMC

Marks JR, Placone J, Hristova K, Wimley WC. Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. J Am Chem Soc. 2011 Jun 15;133(23):8995-9004. doi PubMed PMC

He L, Hoffmann AR, Serrano C, Hristova K, Wimley WC. High-throughput selection of transmembrane sequences that enhance receptor tyrosine kinase activation. J Mol Biol. 2011 412(1):43-54. doi PubMed PMC (Collaboration with the Hristova Lab at Johns Hopkins)

Rathinakumar R, Wimley WC. (2010) High-throughput discovery of broad-spectrum peptide antibiotics. FASEB J. 2010 Sep;24(9):3232-8. doi PubMed PMC