Show simple item record

dc.contributor.advisorLaurence, Jennifer S
dc.contributor.authorKrause, Mary Elizabeth
dc.date.accessioned2012-11-26T20:57:31Z
dc.date.available2012-11-26T20:57:31Z
dc.date.issued2011-05-31
dc.date.submitted2011
dc.identifier.otherhttp://dissertations.umi.com/ku:11481
dc.identifier.urihttp://hdl.handle.net/1808/10428
dc.description.abstractThe 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.
dc.format.extent122 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectChemistry
dc.subjectBiochemistry
dc.subjectInorganic chemistry
dc.subjectChiral inversion
dc.subjectMetal abstraction peptide
dc.subjectNickel
dc.subjectNi-ncc
dc.subjectPeptide-metal complex
dc.subjectSquare-planar
dc.titleStructure/Function Relationships in Nickel-Peptide Complexes: Impact of the Primary Coordination Sphere on Square-Planar Nickel Chemistry
dc.typeDissertation
dc.contributor.cmtememberJackson, Timothy A.
dc.contributor.cmtememberSchowen, Richard L.
dc.contributor.cmtememberScott, Emily E.
dc.contributor.cmtememberSiahaan, Teruna
dc.thesis.degreeDisciplineChemistry
dc.thesis.degreeLevelPh.D.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record