- SNP discrimination by tolane-modified peptide nucleic acids: Application for the detection of drug resistance in pathogens
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During the treatment of viral or bacterial infections, it is important to evaluate any resistance to the therapeutic agents used. An amino acid substitution arising from a single base mutation in a particular gene often causes drug resistance in pathogens. Therefore, molecular tools that discriminate a single base mismatch in the target sequence are required for achieving therapeutic success. Here, we synthesized peptide nucleic acids (PNAs) derivatized with tolane via an amide linkage at the N-terminus and succeeded in improving the sequence specificity, even with a mismatched base pair located near the terminal region of the duplex. We assessed the sequence specificities of the tolane-PNAs for single-strand DNA and RNA by UV-melting temperature analysis, thermodynamic analysis, an in silico conformational search, and a gel mobility shift assay. As a result, all of the PNA-tolane derivatives stabilized duplex formation to the matched target sequence without inducing mismatch target binding. Among the different PNA-tolane derivatives, PNA that was modified with a naphthyl-type tolane could efficiently discriminate a mismatched base pair and be utilized for the detection of resistance to neuraminidase inhibitors of the influenza A/H1N1 virus. Therefore, our molecular tool can be used to discriminate single nucleotide polymorphisms that are related to drug resistance in pathogens.
- Ebara, Yasuhito,Hayashi, Tenko,Hori, Sakiko,Kaihatsu, Kunihiro,Kato, Nobuo,Ogata, Katsuya,Okazaki, Miku,Sawada, Shinjiro,Takagi, Kenji
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- A rapid and efficient Sonogashira protocol and improved synthesis of free fatty acid 1 (FFA1) receptor agonists
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(Chemical Equation Presented) Aprotocol for rapid and efficient Pd/Cu-catalyzed coupling of aryl bromides and iodides to terminal alkynes has been developed with use of 2-(di-tert-butylphosphino)-N-phenylindole (cataCXium PIntB) as ligand inTMEDA and wate
- Christiansen, Elisabeth,Due-Hansen, Maria E.,Ulven, Trond
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supporting information; experimental part
p. 1301 - 1304
(2010/04/26)
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- COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES
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There is provided novel compounds capable of modulating the G-protein-coupled receptor GPR40, compositions comprising the compounds, and methods for their use for controlling insulin levels in vivo and for the treatment of conditions such as type Il diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.
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Page/Page column 40
(2010/04/03)
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- Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA1/GPR40), a potential target for the treatment of type II diabetes
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A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA1) has been discovered and explored. The preferred compound 20 (TUG-424, EC50 = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA1 in metabolic diseases such as diabetes or obesity.
- Christiansen, Elisabeth,Urban, Christian,Merten, Nicole,Liebscher, Kathrin,Karlsen, Kasper K.,Hamacher, Alexandra,Spinrath, Andreas,Bond, Andrew D.,Drewke, Christel,Ullrich, Susanne,Kassack, Matthias U.,Kostenis, Evi,Ulven, Trond
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supporting information; experimental part
p. 7061 - 7064
(2009/11/30)
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