Enhancing β3-Peptide Bundle Stability by Design

Authors

  • Cody J. Craig,

    1. Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-8107 (USA)
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  • Dr. Jessica L. Goodman,

    1. Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-8107 (USA)
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  • Prof. Alanna Schepartz

    Corresponding author
    1. Departments of Chemistry and Molecular, Cellular and Developmental Biology, Yale University, 225 Prospect Street, New Haven, CT 06520-8107 (USA), Fax: (+1) 203-432-3486
    • Departments of Chemistry and Molecular, Cellular and Developmental Biology, Yale University, 225 Prospect Street, New Haven, CT 06520-8107 (USA), Fax: (+1) 203-432-3486
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Abstract

We reported recently that certain β3-peptides self-assemble in aqueous solution into discrete bundles of unique structure and defined stoichiometry. The first β-peptide bundle reported was the octameric Zwit-1F, whose fold is characterized by a well-packed, leucine-rich core and a salt-bridge-rich surface. Close inspection of the Zwit-1F structure revealed four nonideal interhelical salt-bridge interactions whose heavy atom–heavy atom distances were longer than found in natural proteins of known structure. Here we demonstrate that the thermodynamic stability of a β-peptide bundle can be enhanced by optimizing the length of these four interhelical salt bridges. Combined with previous work on the role of internal packing residues, these results provide another critical step in the “bottom-up” formation of β-peptide assemblies with defined sizes, reproducible structures, and sophisticated function.

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