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    Synthetic and computational efforts toward the understanding and development of novobiocin-derived inhibitors of Hsp90

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    Lubbers_ku_0099M_10012_DATA_1.pdf (2.422Mb)
    Issue Date
    2008-01-01
    Author
    Lubbers, Donna Jeanne
    Publisher
    University of Kansas
    Format
    101 pages
    Type
    Thesis
    Degree Level
    M.S.
    Discipline
    Medicinal Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    As C−terminal inhibitors of a 90−kDa heat shock protein (Hsp90), novobiocin and its derivatives are a significant part of an emerging class of cancer chemotherapeutic agents. Previous studies have shown that analogues of the coumarin and benzamide moieties of novobiocin exhibit more than a 1000−fold improvement in activity over the parent compound. This thesis describes synthetic efforts toward the completion of noviose mimics to determine moieties that are critical for binding or can be altered for improved activity. Additionally, in the absence of a co−crystal structure for the Hsp90 C−terminus, there is a need to develop an accurate model to assist in efficient drug design. This work describes the use of molecular modeling and docking software to design new, potentially useful models of C−terminal interactions.
    URI
    http://hdl.handle.net/1808/4338
    Collections
    • Theses [3711]
    • Medicinal Chemistry Dissertations and Theses [58]
    • Medicinal Chemistry Dissertations and Theses [58]

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    785-864-8983
    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    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
     

     

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