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Full-Text Articles in Biochemistry

Scale Up Isolation Of Aaptamine For In Vivo Evaluation Indicates Its Neurobiological Activity Is Linked To The Delta Opioid Receptor, Nicole L. Mcintosh, Eptisam Lambo, Laura Millan-Lobo, Fei Li, Li He, Phillip Crews, Jennifer L. Whistler, Tyler Johnson Mar 2019

Scale Up Isolation Of Aaptamine For In Vivo Evaluation Indicates Its Neurobiological Activity Is Linked To The Delta Opioid Receptor, Nicole L. Mcintosh, Eptisam Lambo, Laura Millan-Lobo, Fei Li, Li He, Phillip Crews, Jennifer L. Whistler, Tyler Johnson

Tyler Johnson

Opioid receptors belong to the large superfamily of seven transmembrane-spanning (7TM) G protein-coupled receptors (GPCRs). As a class, GPCRs are of fundamental physiological importance mediating the actions of the majority of known neurotransmitters and hormones. The Mu, Delta, and Kappa (MOP, DOP, KOP) opioid receptors are particularly intriguing members of this receptor family as they are the targets involved in many neurobiological diseases such as addiction, pain, stress, anxiety, and depression. Recently we discovered that the aaptamine class of marine sponge derived natural products exhibit selective agonist activity in vitro for the DOP versus MOP receptor. Our findings may explain …


Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2019

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Tyler Johnson

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A Beniddir, Maique W Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S Butler, Robert J Capon, Young H Choi, David Coppage, Phillip Crews, Michael T Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M Egan, Mary J Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G I Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli Feb 2019

The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A Beniddir, Maique W Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S Butler, Robert J Capon, Young H Choi, David Coppage, Phillip Crews, Michael T Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M Egan, Mary J Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G I Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli

Tyler Johnson

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data …


The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A Valeriote, Phillip Crews Feb 2019

The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A Valeriote, Phillip Crews

Tyler Johnson

Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Feb 2019

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Tyler Johnson

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester Feb 2019

Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester

Tyler Johnson

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews Feb 2019

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews

Tyler Johnson

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou Feb 2019

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou

Tyler Johnson

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn Feb 2019

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn

Tyler Johnson

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …


Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A Valeriote, Phillip Crews Feb 2019

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A Valeriote, Phillip Crews

Tyler Johnson

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …


Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L Mooberry Feb 2019

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L Mooberry

Tyler Johnson

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …


Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman Feb 2019

Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman

Tyler Johnson

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors …