KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Molecular Biosciences
    • Molecular Biosciences Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Molecular Biosciences
    • Molecular Biosciences Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

    Thumbnail
    View/Open
    Sievers_2014.pdf (1002.Kb)
    Issue Date
    2011-06-07
    Author
    Sievers, Stuart A.
    Karanicolas, John
    Chang, Howard W.
    Zhao, Anni
    Jiang, Lin
    Zirafi, Onofrio
    Stevens, Jason T.
    Münch, Jan
    Baker, David
    Eisenberg, David
    Publisher
    Nature Publishing Group
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Metadata
    Show full item record
    Abstract
    Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures.
    URI
    http://hdl.handle.net/1808/14689
    DOI
    https://doi.org/10.1038/nature10154
    Collections
    • Molecular Biosciences Scholarly Works [598]
    Citation
    Sievers et al. "Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation." Nature. Jul 7, 2011; 475(7354): 96–100. http://dx.doi.org/10.1038/nature10154

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    Login

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps