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- 2005 HighWireInternational Commission on Radiation Units and Measurements.Also available: Print – 2005
- 2010John Vincent Mulcahy.Voltage-gated sodium ion channels are integral membrane proteins most commonly associated with the propagation of action potentials along electrically conducting cells. Nine distinct mammalian isoforms exist, which vary in their primary sequence, gating properties and tissue distribution. Efforts to deconvolute the physiological roles of each isoform through genetic methods, including knockout and gene silencing, are complicated by issues of redundancy and compensatory upregulation of related isoforms. Here we present new strategies and methods for the synthesis of a class of small molecule sodium channel inhibitors, the paralytic shellfish poisons. Methods for the construction of cyclic 5-membered guanidines from acyclic precursors through intramolecular C--H amination and a total synthesis of the paralytic shellfish poison (+)-gonyautoxin 3 are described. It is our vision that these developments will ultimately lead to new small molecule probes designed to help answer fundamental questions regarding sodium ion channel structure and diversity.
- v. 78, 80, 89, 93, 95-96, 100, 102-103, 105, 108-117, 119-, 1999- CRCnetBaseSchick, Martin J.
- 2008 SpringerKailash C. Khulbe, C.Y. Feng, Takeshi Matsuura.
- 2012Elizabeth Josephine Beans.The theme of this work is to utilize hypothesis driven synthetic manipulation to enhance our understanding of the biological effects of prostratin and its highly potent analogs, and to utilize this understanding for the improvement of the therapeutic properties thereof. Prostratin, a natural product activator of protein kinase C (PKC), is a molecule of interest for targeting latent HIV, the primary obstacle to HIV eradication in infected individuals on effective highly active antiretroviral therapy. Chapter one describes the current state of the HIV pandemic, therapeutic strategies, prospects for a cure, and clinical studies toward immune activation therapy. Chapter two is a seminal and complete analysis of the biological effects of prostratin, a natural product candidate for immune activation therapy. Chapter three presents the design, synthesis, and evaluation of highly potent analogs of prostratin via an efficient semi-synthetic route. Chapter four presents the design and synthesis of isotopically labeled prostratin analogs to be utilized in solid-state NMR studies probing the active conformation of the PKC/activator complex in its membrane associated state. Chapter five presents the design, synthesis, and evaluation of prodrugs of prostratin and prostratin analogs for the optimization of pharmacologic properties.
- An online journal and ebook service of the Thieme Publishing Group. The ebook package is also called Thieme Clinical Collections.
- 2008 CRCnetBASE[edited by] Monika Waksmundzka-Hajnos, Joseph Sherma, Teresa Kowalska.
- 2005- WileyUllmann, Fritz.Covers science and technology in all areas of industrial chemistry, containing nearly 1000 major articles with more than 16 million words, nearly 10,000 tables, 30,000 figures, and literature sources and cross-references. It also includes full text index, author index, CAS registry number index, and keyword index.
- 2008 CRCnetBASEHugh Cartwright ; chapter 10, Evolvable developmental systems, contributed by Nawwaf Kharma.
- 2010Justin David Litchfield.Several methods of examining the structure and function of voltage-gated ion channels are described. The first part of this work involves synthetic small molecules based on the structure of (+)-saxitoxin, a marine neurotoxin. (+)-saxitoxin interacts with the pore of the voltage-gated sodium (NaV ) channel to prevent the passage of ions. A scaffold was designed to be modular, synthetically facile, and contain the functionality that had been implicated in the previous literature. Several members of this family of molecules were produced, and they were assayed for occlusion of sodium current (INa). The second part of this work examines the gating kinetics of voltage-gated potassium (KV) channels. 6-bromo-mercaptotryptamine (BrMT) is a marine neurotoxin that has been shown to alter the gating kinetics of KV channels. Specifically, BrMT affects the early, typically independent steps of KV gating by stabilizing the resting state of some number of the subunits. A family of small molecules was designed and synthesized that would examine the functional effects of different parts of the BrMT molecule. BrMT is a dimer containing three key functional groups: a halogenated indole, a pendant ethyl-amine, and a disulfide linker. Variance at all these positions was examined, and each had different effects. Notably, one of the variants, in which the disulfide linker was substituted for an oxy-bismethyl ether linker, affects KV gating in a different way from BrMT. Alternate models of gating in the presence of this novel analog are discussed.
- 2011Mari Iwamoto.The ability to make specific perturbations to biological molecules in a cell or organism is a central experimental strategy in modern research biology. Chemical approaches to probe biological function have greatly contributed to the understanding of protein functions. While small-molecule inhibitors offer rapid and reversible control of protein functions, identification and development of specific inhibitors for every protein of interest remains a challenge. In the past decade, numerous technologies have been developed that combine genetic with chemical methods to create conditional protein control systems with impeccable specificity. These systems include inducible protein localization using chemical inducer of dimerization, such as rapamycin, and inducible protein stabilization system such as our destabilizing domain (DD) technology previously developed by L. Banaszynski. Highly specific, high-affinity protein-ligand interactions are key to their effectiveness. In this thesis, three technologies that utilize highly specific protein-ligand interactions are discussed. The first chapter of this thesis focuses on the development of a general technique in which the stability of a specific protein is regulated by a cell-permeable small molecule. Mutants of E. coli dihydrofolate reductase (ecDHFR) were engineered to have ligand-dependent stability, and when this destabilizing domain is fused to a protein of interest, the instability is conferred to the fused protein resulting in rapid degradation of the entire fusion protein. A small-molecule ligand trimethoprim (TMP) stabilized the destabilizing domain in a rapid, reversible and dose-dependent manner, and protein levels in the absence of TMP were barely detectable. The ability of TMP to cross the blood-brain barrier enabled the tunable regulation of YFP expressed rat striatum. The second chapter of this thesis describes the development of a technique in which a protein of interest is degraded in the presence of a ligand. In this system, we regulated the stability of a receptor protein of an E3 ligase complex using the previously developed destabilizing domains. A DD-fused receptor protein cannot recruit the substrate to the E3 ubiquitin ligase in the absence of ligand. Upon addition of ligand, the receptor protein is stabilized and can successfully promote ubiquitination and degradation of the substrate protein. We used HIV-1 Vif protein, a receptor protein of the Cul5 E3 ligase complex, and its substrate, human APOBEC3G. We were able to induce degradation of GFP fused APOBEC3G upon addition of ligand. Degradation of GFP occurred rapidly, tunably, and reversibly. The advantage of this system over the DD technology is that it does not require continuous administration of the ligand until the desired experimental window and is thus better suited for in vivo applications. By limiting the dosage to only during the knockout window, the cost of dosing is dramatically decreased and side effects from long-term administration of ligand can be minimized. The third and last chapter of this thesis describes an attempt to develop a new approach to induce genome modification at a specific site with high efficiency in mammalian cell lines. While there are several successful nuclease-based gene-targeting approaches that exist today, these technologies require extensive engineering and screening to isolate efficient and specific nucleases that bind to the target sites. Our strategy was to simplify the design of DNA targeting domains by using an oligonucleotide analogue, peptide nucleic acid (PNA). PNAs incorporate DNA bases on peptide backbones and make base-specific contacts with the target DNA site. The PNA domain is coupled to TMP, which then allows recruitment of the nuclease domain fused to ecDHFR. The nuclease domain is made up of a single-chain, pseudohomodimer FokI catalytic domain that non-specifically cleaves the DNA. We could not produce any recombination activity in cell. However, in vivo experiments revealed successful target DNA binding by the PNA, as well as TMP-PNA/ecDHFR-FokI binding.
- 2012 Springer Protocolsedited by Emilio Badoer.Multiple immunohistochemical labelling of peripheral neurons / Ian L. Gibbins -- Combined in situ hybridization and immunohistochemistry in rat brain tissue using digoxigenin-labeled riboprobes / Natasha N. Kumar, Belinda R. Bowman, and Ann K. Goodchild -- In situ hybridization within the CNS tissue : combining in situ hybridization with immunofluorescence / Dominic Bastien and Steve Lacroix -- Visualizing GABA[subscriptβ] receptor internalization and intracellular trafficking / Paola Ramoino [and others] -- Using total internal reflection fluorescence microscopy (TIRFM) to visualise insulin action / James G. Burchfield, Jamie A. Lopez, and William E. Hughes -- Live-cell quantification of mitochondrial functional parameters / Marco Nooteboom [and others] -- Functional imaging using two-photon microscopy in living tissue / Ivo Vanzetta [and others] -- Calcium imaging techniques in vitro to explore the role of dendrites in signaling physiological action potential patterns / Audrey Bonnan, Benjamin Grewe, and Andreas Frick -- Juxtacellular labeling in combination with other histological techniques to determine phenotype of physiologically identified neurons / Ruth L. Stornetta -- Visualization of activated neurons involved in endocrine and dietary pathways using GFP-expressing mice / Rim Hassouna [and others] -- Use and visualization of neuroanatomical viral transneuronal tracers / J. Patrick Card and Lynn W. Enquist -- Visualisation of thermal changes in freely moving animals / Daniel M.L. Vianna and Pascal Carrive -- Perfusion magnetic resonance imaging quantification in the brain / Fernando Calamante.
- 2007 WileyAlbrecht Messerschmidt.Part I. Principles and Methods -- Chapter 1. Introduction, p. 1-22 -- Chapter 2. Experimental Techniques, p. 23-44 -- Chapter 3. Principles of X-Ray Diffraction by a Crystal, p. 45-79 -- Chapter 4. Diffraction Data Evaluation, p. 81-97 -- Chapter 5. Methods for Solving the Phase Problem, p. 99-139 -- Chapter 6. Phase Improvement by Density Modification and Phase Combination, p. 141-156 -- Chapter 7. Model Building and Refinement, p. 157-185 -- Chapter 8. Crystal Structure Determination of the Time-Course of Reactions and of Unstable Species, p. 187-202 -- Chapter 9. Structural Genomics, p. 203-220 -- Part II. Practical Examples -- Chapter 10. Data Evaluation, p. 223-238 -- Chapter 11. Determination of Anomalous Scatterer or Heavy Atom Positions, p. 239-251 -- Chapter 12. MIRAS and MAD Phasing with the Program SHARP, p. 253-259 -- Chapter 13. Molecular Replacement, p. 261-266 -- Chapter 14. Averaging about Non-Crystallographic Symmetry (NCS) for 4-BUDH, p. 267-275 -- Chapter 15. Model Building and More, p. 277-291
- Harrison's Principles of Internal Medicine
- AAP Red Book Online
- Robbins & Cotran Pathologic Basis of Disease
- Sabiston Textbook of Surgery
- Nelson's Textbook of Pediatrics
- Surgical Exposures in Orthopaedics
- Mandell, Douglas, & Bennett's Principles & Practice of Infectious Diseases
- Red Book Online
- ICU Book
- Primary Care Medicine
- Campbell-Walsh Urology
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