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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 ...
Novel DNA Adducts- Chemical Reactions that Model the Generation of interstrand cross-links between a Guanine Residue and a 3'-alkenal end product in duplex DNA
(University of Missouri--Columbia, 2019)
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Modification of DNA by chemicals produced lethal biological effects such as carcinogenesis, cytotoxicity, etc. Abasic site (Ap site) can ...
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 ...
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 ...
Synthesis and properties of small molecules designed to covalently capture native and oxidized forms of protein tyrosine phosphatase 1B (PTP1B)
(University of Missouri--Columbia, 2016)
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Protein tyrosine phosphatase 1B (PTP1B) is a validated target for the treatment of type 2 diabetes and obesity. The discovery of selective inhibitors ...
Small molecule-based approaches toward elucidation of structure and properties of abasic site-derived interstrand DNA crosslinks /
(University of Missouri--Columbia, 2016)
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Damage to DNA is both a naturally occurring and environmentally induced process that can have serious biological consequences, such as mutation and ...
Studies of natural products that reveal novel strategies for efficient modification of DNA
(University of Missouri--Columbia, 2006)
DNA is the central molecule in cells. The correct function of cells depends on the structure of DNA. DNA damaging natural products often show cytotoxic or mutagenic properties, which many times land them medicinal value ...
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 ...
Synthesis of exo-affinity labeling agents of protein tyrosine phosphatase non-receptor type 1
(University of Missouri--Columbia, 2015)
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator in the insulin signaling cascade. A lot of research has focused on inhibiting PTP1B ...
On the kinetics and mechanisms associated with covalent inactivation of protein tyrosine phosphatase 1b (ptp1b) by dietary phytochemicals and affinity labeling molecules
(University of Missouri--Columbia, 2015)
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Phytochemical are compounds that occur naturally in plants. These compounds are what give many foods their distinct color and flavor. There are five ...
Toward selective inactivation of protein tyrosine phosphatase 1B via exo-affinity labeling agents
(University of Missouri--Columbia, 2014)
Exo-affinity labeling agents are compounds that achieve selectivity by modifying non-catalytic residues in a protein. They have been utilized as tools in molecular biology and to make successful drugs for protein targets. ...
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 ...
Synthesis and trapping of an active site mimic of oxidized PTP-1B by small molecule nucleophiles
(University of Missouri--Columbia, 2014)
Hypoxia selective DNA alkylating analogs of tirapazamine and Ap-derived DNA interstrand cross-linksHypoxia 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 ...
Generation of DNA-damaging reactive oxygen species via the autoxidation of hydrogen sulfide under physiologically relevant conditions
(University of Missouri--Columbia, 2014)
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), ...
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 ...
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 ...
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 ...
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 ...