On Abietic Acid and Related Resin Acids from Oleoresin of American Conifers PDF Download
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Author: Orville Andrew Beath
Publisher:
ISBN:
Category :
Languages : en
Pages : 140
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Author: Orville Andrew Beath
Publisher:
ISBN:
Category :
Languages : en
Pages : 140
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Author: Nina Ottosson
Publisher: Linköping University Electronic Press
ISBN: 917685521X
Category :
Languages : en
Pages : 66
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Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures. Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from this position, electrostatically facilitate the movement of the voltage-sensor, thereby opening the channel. However, PUFAs affect a wide range of ion channels, making it difficult to use them as pharmaceutical drugs; it would be desirable to find smallmolecule compounds with an electrostatic, PUFA-like mechanism of action. The aim of the research leading to this thesis was to find, characterize, and refine drug candidates capable of electrostatically opening a Kv channel. The majority of the experiments were performed on the cloned Shaker Kv channel, expressed in oocytes from the frog Xenopus laevis, and the channel activity was explored with the two-electrode voltage-clamp technique. By systematically mutating the extracellular end of the channel’s voltage sensor, we constructed a highly PUFAsensitive channel, called the 3R channel. Such a channel is a useful tool in the search for electrostatic Kv-channel openers. We found that resin acids, naturally occurring in tree resins, act as electrostatic Shaker Kv channel openers. To explore the structure-activity relationship in detail, we synthesized 120 derivatives, whereof several were potent Shaker Kv channel openers. We mapped a common resin acidbinding site to a pocket formed by the voltage sensor, the channel’s third transmembrane segment, and the lipid membrane, a principally new binding site for small-molecule compounds. Further experiments showed that there are specific interactions between the compounds and the channel, suggesting promises for further drug development. Several of the most potent Shaker Kv channel openers also dampened the excitability in dorsal-root-ganglion neurons from mice, elucidating the pharmacological potency of these compounds. In conclusion, we have found that resin-acid derivatives are robust Kv-channel openers and potential drug candidates against diseases caused by hyperexcitability, such as epilepsy.
Author: Arlie William Schorger
Publisher:
ISBN:
Category : Conifers
Languages : en
Pages : 56
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Author: Society of Chemical Industry (Great Britain)
Publisher:
ISBN:
Category : Chemistry, Technical
Languages : en
Pages : 2436
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Author:
Publisher:
ISBN:
Category : Chemical industry
Languages : en
Pages : 776
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Author: Tatjana Stevanovic
Publisher: CRC Press
ISBN: 1498775705
Category : Science
Languages : en
Pages : 315
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This book presents the chemical properties of lignocellulosic fibers, knowledge of which is essential for innovation and sustainable development of their transformation. Thermochemical transformation of wood and other lignocellulosics is presented to highlight its volatile, liquid and solid products and their novel applications. Forest biorefinery is described to emphasize the new products from lignocellulosic constituents, both structural (cellulose, hemicelluloses and lignins) and those extraneous to cell walls-extractives. New developments in cellulose technology related to nanocellulose are discussed in relation to new applications. Industrial lignins are presented in detail, both in terms of extraction procedures from spent liquors and structural characterization of the isolated lignins. Application of lignocellulosic biopolymers in new composite materials, or in biomaterials for medicinal purposes, and in solid wood preservation, are described. The example of an industrial biorefinery installed in southwestern France more than 40 years ago is presented.
Author:
Publisher:
ISBN:
Category : Chemistry, Technical
Languages : en
Pages : 1070
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Author:
Publisher:
ISBN:
Category : Chemistry, Technical
Languages : en
Pages : 1064
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Author:
Publisher:
ISBN:
Category : Chemistry
Languages : en
Pages : 1620
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Author:
Publisher:
ISBN:
Category : Chemistry, Technical
Languages : en
Pages : 528
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