Browsing Graduate School - MU Theses and Dissertations (MU) by Thesis Advisor "Gates, Kent S. (Kent Stephen), 1962-"
Now showing items 1-20 of 29
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Biologically relevant chemistry of sulfur heterocycles : from redox regulation of PTP1B to the biological activity of s-deoxy leinamycin
(University of Missouri--Columbia, 2008)Protein tyrosine phosphatase 1B (PTP1B) is an important member of protein tyrosine phosphatase (PTPs) family that shares a conserved catalytic cysteine thiol residue. PTP1B acts as a negative regulator of insulin mediated ... -
Bioreductive metabolism of small molecule nitroaromatics and N-oxides in hypoxia
(University of Missouri--Columbia, 2012)Hypoxia in tumors causes adverse effects to therapy and negatively impacts on patient prognosis. Identification and quantification of hypoxia is considered to have a strong impact on treatments in tumor therapy. Fluorescent-based ... -
Chemical and strutural properties of DNA-abasic site cross-links
(University of Missouri--Columbia, 2014)Here, we report on the formation of DNA interstrand cross-links. These cross-links form from abasic sites, an endogenous type of DNA damage. We have utilized gel electrophoresis, NMR, mass spectrometry and liquid chromatography ... -
Chemical mechanisms of DNA damaging natural products
(University of Missouri--Columbia, 2011)[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Natural products provide both novel molecular structures and new mechanisms that have significant therapeutical implications. The work described here ... -
Chemical mechanisms underlying the medicinal activity of metabolically-activated N-oxide antitumor agents
(University of Missouri--Columbia, 2008)Tirapazamine (TPZ) belongs to a new class of bio-reductively activated hypoxiaselective anti-cancer agents and is currently undergoing in various clinical trials including Phase I, II and III. Anti-cancer activity of TPZ ... -
Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double and single-stranded DNA
(University of Missouri--Columbia, 2014)[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Hydralazine is an antihypertensive agent that displays both mutagenic and epigenetic properties. Here, we provide evidence that medicinally-relevant ... -
The development of exo-affinity labeling agents, inactivators of protein tyrosine phosphatase 1B
(University of Missouri--Columbia, 2016)The phosphorylation of a tyrosine substrate is one of the most crucial reactions that regulate numerous biological processes. The phosphorylation is controlled by protein tyrosine kinases (PTKs) and protein tyrosine ... -
The development of the first generation of exo-affinity labeling agents, inactivators of protein tyrosine phosphatase 1B
(University of Missouri--Columbia, 2014)Type II Diabetes (T2DB) is one of the worldwide problems characterized by ineffective insulin signal transduction as a result of insulin resistance and impaired glucose homeostasis. Protein Tyrosine Phosphatase 1B (PTP1B), ... -
Discovery of small molecules that regulate the activity of protein tyrosine phosphatases
(University of Missouri--Columbia, 2011)[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Protein tyrosine phosphatases (PTPs) are cysteine-dependent enzymes responsible for dephosphorylating phosphotyrosine residues through a phosphocysteine ... -
Effects of local sequence on the formation of interstrand DNA cross-links derived from the reaction of an abasic site with a cytosine residue on the opposing strand
(University of Missouri--Columbia, 2019)DNA Interstrand Cross-Links are of special concern due to the difficulty of repair and cytotoxicity of cells associated with these lesions. Interstrand Cross-Links between abasic sites and native nucleobases has shown ... -
Fast, inexpensive, high-yielding, site-selective, chemical synthesis of cross-linked DNA duplexes via hydrazone formation between N[superscript 4]-aminocytidine and Ap-sites
(University of Missouri--Columbia, 2017)[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] DNA is the central molecule of biology as it stores the genetic information for cells to properly function and develop. Modifications to the DNA can ... -
Generation of DNA-damaging reactive oxygen species via the autoxidation of hydrogen sulfide under physiologically relevant conditions
(University of Missouri--Columbia, 2014) -
Hypoxia selective DNA alkylating analogs of tirapazamine and Ap-derived DNA interstrand cross-links
(University of Missouri--Columbia, 2014)Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide, TPZ) is a heterocyclic di-N-oxide that can be selectively reduced enzymatically in oxygen-poor (hypoxic) cells commonly associated with solid tumors. This reduction ... -
Inactivation of protein tyrosine phosphatases by endogenous and dietary agents
(University of Missouri--Columbia, 2009)Protein tyrosine phosphatases are a class of enzymes that control a number of critical signaling pathways inside cells. We have discovered a number of dietary and endogenous agents that are capable of modifying these ... -
Investigation of the kinetcis [sic] and mechanisms of the inactivation of PTP-SHP2 peroxycarbonate and phytochemicals
(University of Missouri--Columbia, 2012)Protein tyrosine phosphatases (PTPs) have a catalytic cysteine in their active site, and have a phosphor-enzyme intermediate. PTPs work in tandem with protein kinases in order to regulate many cellular signaling pathways. ... -
Investigations into the chemistry of protein tyrosine phosphatase redox regulation
(University of Missouri--Columbia, 2009)Transmission of complex intracellular signals, such as those for glucose uptake or proliferation, is often accomplished through the reversible phosphorylation of specific protein tyrosine residues. This reversible ... -
Kinetics and mechanisms associated with redox regulation of protein tyrosine phosphatase 1B (PTP1B)
(University of Missouri--Columbia, 2015)Here, we report on the kinetics and mechanisms associated with redox regulation of the protein tyrosine phosphatase PTP1B. We determined rates of thiol- and phosphinemediated recovery of catalytic activity from the ... -
Metabolically activated heterocyclic N-oxide compounds for killing and visualizing hypoxic cancer cells
(University of Missouri--Columbia, 2009)Tirapazamine (TPZ) is currently undergoing a variety of phase I, II, and III clinical trials for the treatment of various human cancers. TPZ derives its medicinal activity by inducing DNA damage in poorly oxygenated tumor ... -
Molecular basis of protein tyrosine phosphatase inhibition by biologically important small molecules with relevance to cell signaling pathways
(University of Missouri--Columbia, 2009)Protein tyrosine phosphatase 1B (PTP1B) is an abundant mammalian enzyme and well known to be as a central player in the insulin and leptin signaling pathways. Peracetic acid is a strong oxidant molecule, endogenously ... -
Novel chemical mechanisms of DNA damage by natural products
(University of Missouri--Columbia, 2007)[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Leinamycin is a structurally novel natural product isolated from the Streptomyces with potent antitumor and antibiotic activity. In a thiol rich ...