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Chemistry

2019

Series

Chemistry and Biochemistry Faculty Publications and Presentations

Articles 1 - 7 of 7

Full-Text Articles in Physical Sciences and Mathematics

Ribbon Α-Conotoxin Ktm Exhibits Potent Inhibition Of Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Lisa R. Warner, Matthew D. King, James R. Groome, Owen M. Mcdougal Dec 2019

Ribbon Α-Conotoxin Ktm Exhibits Potent Inhibition Of Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Lisa R. Warner, Matthew D. King, James R. Groome, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3β2-nicotinic acetylcholine receptors (rα3β2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3β2-nAChRs by KTM (IC50 = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC50 = …

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Qualitative Assay To Detect Dopamine Release By Ligand Action On Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Owen M. Mcdougal Dec 2019

Qualitative Assay To Detect Dopamine Release By Ligand Action On Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

A pheochromocytoma of the rat adrenal medulla derived (a.k.a. PC12) cell-based assay for dopamine measurement by luminescence detection was customized for the qualitative evaluation of agonists and antagonists of nicotinic acetylcholine receptors (nAChRs). The assay mechanism begins with ligand binding to transmembrane nAChRs, altering ion flow into the cell and inducing dopamine release from the cell. Following release, dopamine is oxidized by monoamine oxidase generating hydrogen peroxide that catalyzes a chemiluminescence reaction involving luminol and horseradish peroxidase, thus producing a detectable response. Results are presented for the action of nAChR agonists (acetylcholine, nicotine, and cytisine), and antagonists (α-conotoxins (α-CTxs) MII, …

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Steroidal Alkaloid Variation In Veratrum Californicum As Determined By Modern Methods Of Analytical Analysis, Matthew W. Turner, Meagan Rossi, Vannessa Campfield, John French, Ellie Hunt, Emily Wade, Owen M. Mcdougal Sep 2019

Steroidal Alkaloid Variation In Veratrum Californicum As Determined By Modern Methods Of Analytical Analysis, Matthew W. Turner, Meagan Rossi, Vannessa Campfield, John French, Ellie Hunt, Emily Wade, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Veratrum californicum is a rich source of steroidal alkaloids, many of which have proven to be antagonists of the Hedgehog (Hh) signaling pathway that becomes aberrant in over twenty types of cancer. These alkaloids first became known in the 1950's due to their teratogenic properties, which resulted in newborn and fetal lambs developing cyclopia as a result of pregnant ewes consuming Veratrum californicum. It was discovered that the alkaloids in V. californicum were concentrated in the root and rhizome of the plant with much lower amounts of the most active alkaloid, cyclopamine, present in the aerial plant, especially in …

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Radiolysis Of Solid-State Nitrogen Heterocycles Provides Clues To Their Abundance In The Early Solar System, Phillip G. Hammer, Ruiqin Yi, Isao Yoda, H. James Cleaves, Michael P. Callahan Aug 2019

Radiolysis Of Solid-State Nitrogen Heterocycles Provides Clues To Their Abundance In The Early Solar System, Phillip G. Hammer, Ruiqin Yi, Isao Yoda, H. James Cleaves, Michael P. Callahan

Chemistry and Biochemistry Faculty Publications and Presentations

We studied the radiolysis of a wide variety of N-heterocycles, including many of biological importance, and find that the majority are remarkably stable in the solid-state when subjected to large doses of ionizing gamma radiation from a 60Co source. Degradation of N-heterocycles as a function of dose rate and total dose was measured using high performance liquid chromatography with UV detection. Many N-heterocycles show little degradation when γ-irradiated up to a total dose of ~1 MGy, which approximates hundreds of millions of years’ worth of radiation emitted in meteorite parent bodies due to slow radionuclide decay. Extrapolation of …

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Nitrogen Heterocycles Form Peptide Nucleic Acid Precursors In Complex Prebiotic Mixtures, Laura E. Rodriguez, Christopher H. House, Karen E. Smith, Melissa R. Roberts, Michael P. Callahan Jun 2019

Nitrogen Heterocycles Form Peptide Nucleic Acid Precursors In Complex Prebiotic Mixtures, Laura E. Rodriguez, Christopher H. House, Karen E. Smith, Melissa R. Roberts, Michael P. Callahan

Chemistry and Biochemistry Faculty Publications and Presentations

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic …

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Organometallic Compounds As Carriers Of Extraterrestrial Cyanide In Primitive Meteorites, Karen E. Smith, Christopher H. House, Ricardo D. Arevalo Jr., Jason P. Dworkin, Michael P. Callahan Jun 2019

Organometallic Compounds As Carriers Of Extraterrestrial Cyanide In Primitive Meteorites, Karen E. Smith, Christopher H. House, Ricardo D. Arevalo Jr., Jason P. Dworkin, Michael P. Callahan

Chemistry and Biochemistry Faculty Publications and Presentations

Extraterrestrial delivery of cyanide may have been crucial for the origin of life on Earth since cyanide is involved in the abiotic synthesis of numerous organic compounds found in extant life; however, little is known about the abundance and species of cyanide present in meteorites. Here, we report cyanide abundance in a set of CM chondrites ranging from 50 ± 1 to 2472 ± 38 nmol·g−1, which relates to the degree of aqueous alteration of the meteorite and indicates that parent body processing influenced cyanide abundance. Analysis of the Lewis Cliff 85311 meteorite shows that its releasable cyanide …

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Mutagenesis Of Α-Conotoxins For Enhancing Activity And Selectivity For Nicotinic Acetylcholine Receptors, Matthew W. Turner, Leanna A. Marquart, Paul D. Phillips, Owen M. Mcdougal Feb 2019

Mutagenesis Of Α-Conotoxins For Enhancing Activity And Selectivity For Nicotinic Acetylcholine Receptors, Matthew W. Turner, Leanna A. Marquart, Paul D. Phillips, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of marine snails of genus Conus. -CTxs are potent and selective antagonists for a variety of nAChR isoforms. Over the past 40 years, α-CTxs have proven to be valuable molecular probes capable of differentiating between closely related nAChR subtypes and have contributed greatly to understanding the physiological role of nAChRs in the mammalian nervous system. Here, we review the amino acid composition and structure of several α-CTxs …

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