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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 ...
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 ...
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 ...
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 ...
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-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 ...
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. ...
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 ...
Synthesis and trapping of an active site mimic of oxidized PTP-1B by small molecule nucleophiles
(University of Missouri--Columbia, 2014)
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...