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.

    Structure/Function Relationships in Nickel-Peptide Complexes: Impact of the Primary Coordination Sphere on Square-Planar Nickel Chemistry

    Thumbnail
    View/Open
    Krause_ku_0099D_11481_DATA_1.pdf (13.61Mb)
    Issue Date
    2011-05-31
    Author
    Krause, Mary Elizabeth
    Publisher
    University of Kansas
    Format
    122 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    The novel metal-binding tripeptide asparagine-cysteine-cysteine (NCC) is capable of coordinating a metal ion, and we are exploring its use in several biological applications. Different metals may be incorporated into this tag, and when it is placed in line with a peptide or protein that has the potential to be used as a targeting agent, it has the potential to facilitate the diagnosis, treatment, and evaluation of cancers and other diseases. For example, platinum may be used as an anti-cancer therapeutic, whereas nickel generates a catalytic antioxidant. The advantage of this tag is that it is extremely small, is composed of naturally occurring amino acids, and binds metal with unique geometry. Metal binds irreversibly at physiological pH but is released upon modest acidification, as occurs with endocytosis. In order to utilize the tripeptide as a metal-binding tag, it is important to understand the structure, reactivity, and stability of this novel system. Initial studies with nickel established that NCC binds metal with 2N:2S geometry. Electronic absorption, circular dichroism (CD), and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic NiII center bound in square planar geometry. This complex acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD), which catalyzes the disproportionation of superoxide to hydrogen peroxide and molecular oxygen. Changes in the CD signal of Ni-NCC indicate the optical activity of the complex changes over time, but mass spectrometry data show that the mass of the complex is unchanged, which suggests chiral rearrangement of the complex occurs. Performing the reaction in D2O allows incorporation of deuterium into non-exchangeable positions, indicating chiral inversion occurs at two of the alpha carbon atoms in the peptide. Control peptides were also used to verify the chirality of the final nickel-peptide complex is DLD-NCC. Characterization of the NCC sequence within a longer peptide shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent due to bis-amide coordination. Chiral inversion does not happen in the same two positions, though initial studies suggest inversion at a different location in the peptide may occur.
    URI
    http://hdl.handle.net/1808/10428
    Collections
    • Chemistry Dissertations and Theses [336]
    • Dissertations [4474]

    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