Pore-forming peptides could have applications as biotechnological tools in the laboratory or as therapeutics in the clinic. In order to achieve the full potential of pore-forming peptides we are evolving their function and also evolving mechanisms for controlling their activity with pH. Important properties we have evolved include:
•Potent, equilibrium pore-formers
•Formation of macromolecule-sized pores
•Pore formers with beta-sheet or alpha-helix secondary structure
•Macromolecule sized pores with pH-triggered activity |
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
Wiedman G, Fuselier T, He J, Searson PC, Hristova K, Wimley WC. Highly efficient macromolecule-sized poration of lipid bilayers by a synthetically evolved peptide. J Am Chem Soc. 2014 Mar 26;136(12):4724-31. doi. PubMed PMC. Collaboration with the Hristova Lab at Johns Hopkins (Collaboration with the Hristova Lab at Johns Hopkins)
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
Krauson AJ, He J, Wimley WC. Determining the mechanism of membrane permeabilizing peptides: identification of potent, equilibrium pore-formers. Biochim Biophys Acta. 2012 Jul;1818(7):1625-32. doi PubMed PMC |
