KUKU

KU ScholarWorks

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

    Synthesis and Evaluation of Fluorescent Tools for Studies of Cancer Biology

    Thumbnail
    View/Open
    Available after: 2021-08-31 (65.66Mb)
    Issue Date
    2019-08-31
    Author
    Gao, Zhe
    Publisher
    University of Kansas
    Format
    170 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Medicinal Chemistry
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    A key enabling technology in biological sciences involves fluorescent probes. These probes are typically small molecules, proteins, or nucleic acids that either possess intrinsic fluorescence or are linked to a fluorophore that emits photons and can be detected by techniques such as fluorescence spectroscopy, imaging, or flow cytometry. In early-stage drug discovery projects, fluorescent probes can be used to sort and differentiate particular types of cells, conduct high-throughput screening campaigns, and image subcellular compartments. In this dissertation, I describe the use of fluorescent probes to study microtubules and mitochondria in living cells. These structures and organelles are of substantial interest in fundamental cellular biology and as targets of anticancer agents. One of these projects is focused on the anticancer agent Paclitaxel (Taxol). This small molecule that binds microtubules and is one of the most effective treatment for patients with breast, ovarian, and lung cancers. Remarkably, although Taxol can shrink slow-growing tumors in some patients, this drug spares rapidly proliferating cells such as bone marrow cells. This inconsistency has been termed the proliferation rate paradox and is not well understood. To probe the mechanism of action of Taxol, we designed and synthesized a drug-like fluorescent probe termed PB-Gly-Taxol. This compound recapitulates many aspects of the biological properties of Taxol in cells, and provides a new tool to study proliferation rate paradox. In a second project, I describe the discovery of a small molecule termed 2,7-difluoropyronin B that accumulates in hyperpolarized mitochondria of cancer cells. When irradiated with visible blue light, this probe depolarizes mitochondrial membranes, offering a new chemical tool for photochemical control over mitochondrial biology.
    URI
    http://hdl.handle.net/1808/29842
    Collections
    • Dissertations [4474]
    • Medicinal Chemistry Dissertations and Theses [80]

    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

    LoginRegister

    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