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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Hybrid Computational Toxicology Models For Regulatory Risk Assessment, Prachi Pradeep Apr 2015

Hybrid Computational Toxicology Models For Regulatory Risk Assessment, Prachi Pradeep

Dissertations (2009 -)

Computational toxicology is the development of quantitative structure activity relationship (QSAR) models that relate a quantitative measure of chemical structure to a biological effect. In silico QSAR tools are widely accepted as a faster alternative to time-consuming clinical and animal testing methods for regulatory risk assessment of xenobiotics used in consumer products. However, different QSAR tools often make contrasting predictions for a new xenobiotic and may also vary in their predictive ability for different class of xenobiotics. This makes their use challenging, especially in regulatory applications, where transparency and interpretation of predictions play a crucial role in the development of ...


Spectral Characterization Of Cytochromes Cyp11a1 (Aka P450scc) Active Site And Catalytic Intermediates, Qianhong Zhu Apr 2015

Spectral Characterization Of Cytochromes Cyp11a1 (Aka P450scc) Active Site And Catalytic Intermediates, Qianhong Zhu

Dissertations (2009 -)

The Cytochromes P450 are monooxygenases which use dioxygen and endogenous reducing equivalents to generate highly reactive intermediates capable of performing several types of oxidative transformations, most commonly, hydroxylations via the so-called Compound I species. There are two main kinds of mammalian P450s: those functioning in drug metabolism and those that facilitate steroid biosynthesis. Steroidogenic P450s participating in the biosynthesis of steroid hormones are involved in a number of different pathways. CYP11A1, one of the steroidogenic P450s also known as P450scc, is the enzyme that converts cholesterol to pregnenolone through side chain cleavage between carbon 20 and 22. The overall process ...


Investigations Of Synthetic Models Of Mononuclear Nonheme Iron Dioxygenases, Michael Bittner Jul 2014

Investigations Of Synthetic Models Of Mononuclear Nonheme Iron Dioxygenases, Michael Bittner

Dissertations (2009 -)

Ring cleaving dioxygenases, such as o-aminophenol dioxygenase (APDO) and extradiol catechol dioxygenases (CatD), play an important role in human metabolism and the degradation of aromatic pollutants, yet questions still remain concerning the enzymatic mechanisms. One area of the catalytic cycle that remains controversial is the geometric and electronic structure of the intermediate formed after O2 binding to the Fe(II) centers. Synthetic model systems can be useful for studying enzyme active sites, as they are easier to modify and characterize than the enzymes themselves. However, synthetic models of APDOs have been relatively rare thus far. We prepared several monoiron ...


Probing The Human Estrogen Receptor-Α Binding Requirements For Phenolic Mono- And Di-Hydroxyl Compounds: A Combined Synthesis, Binding And Docking Study, Christopher Mccullough, Terrence S. Neumann, Jayapal Reddy Gone, Zhengjie He, Christian Herrild, Julie Lukesh, Rajesh K. Pandey, William A. Donaldson, Daniel S. Sem Jan 2014

Probing The Human Estrogen Receptor-Α Binding Requirements For Phenolic Mono- And Di-Hydroxyl Compounds: A Combined Synthesis, Binding And Docking Study, Christopher Mccullough, Terrence S. Neumann, Jayapal Reddy Gone, Zhengjie He, Christian Herrild, Julie Lukesh, Rajesh K. Pandey, William A. Donaldson, Daniel S. Sem

Chemistry Faculty Research and Publications

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα ...


Nmr And Computational Characterization Of Protein Structure And Ligand Binding, Terrence Neumann Oct 2013

Nmr And Computational Characterization Of Protein Structure And Ligand Binding, Terrence Neumann

Dissertations (2009 -)

Nuclear magnetic resonance (NMR) techniques combined with computational methods such as docking and cheminformatics were used to characterize protein structure and ligand binding. The thioredoxin system of Mycobacterium tuberculosis consists of a thioredoxin reductase and at least three thioredoxins. This system is responsible for maintaining the cellular protein thiol redox state in normal state. This maintenance is important as the bacterium is engulfed by the human macrophage. Here it is bombarded by reactive oxygen and nitrogen species in an attempt to disrupt normal cellular function in part by perturbing the protein thiols. To this end, the solution structures of the ...