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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 ...
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 ...
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 ...
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 ...
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 ...
Oxidative DNA damage by 1-hydroxyphenazine, virulence factor of Pseudomonas aeruginosa : towards a molecular understanding of the bacterial virulence factor 1-hydroxyphenazine
(University of Missouri--Columbia, 2008)
1-Hydroxyphenazine is a secondary metabolite and virulence factor of Pseudomonas aeruginosa. This organism colonizes the airways of the patients of cystic fibrosis and causes progressive destruction of the airways. It is ...
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 ...
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 ...
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 ...
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 ...
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. ...
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. ...