- COMPOSITIONS FOR TRANSFECTING A NUCLEIC ACID MOLECULE INTO A CELL COMPRISING HETEROCYCLIC COMPOUNDS GRAFTED TO A CATIONIC POLYMER, AND THEIR APPLICATIONS
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The present invention relates to compositions for transfecting a nucleic acid molecule into a cell and their applications. The present invention is directed to a composition suitable for transfecting a nucleic acid molecule into a cell, preferably a eukaryotic cell, comprising (i) at least one compound of general formula (II) or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or an acceptable salt thereof, and (ii) an acceptable excipient, buffering agent, cell culture medium, or transfection medium, wherein Y11, Y22, Y33, Z11, Z22, Z33, Z44, Z55, Z66, Z77, X11, X22, R33, P++, R, T, U and V are as defined in the description. The present invention also relates to uses of said composition and to a method for in vitro or ex vivo transfection of live cells.
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Page/Page column 43; 44; 49; 50
(2021/02/12)
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- Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
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Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.
- De Vita, Elena,Schüler, Peter,Lovell, Scott,Lohbeck, Jasmin,Kullmann, Sven,Rabinovich, Eitan,Sananes, Amiram,He?ling, Bernd,Hamon, Veronique,Papo, Niv,Hess, Jochen,Tate, Edward W.,Gunkel, Nikolas,Miller, Aubry K.
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p. 8859 - 8874
(2018/10/09)
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- A benzimidazole compound and its preparation method and application
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Provided are 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole and a preparation method and an application thereof. The preparation method comprises the steps: firstly, with a benzimidazole compound and potassium chloroacetate as raw materials and ethanol as a solvent, carrying out a reflux reaction to obtain a 1-carboxymethyl-benzimidazole compound; then with polyphosphoric acid, the 1-carboxymethyl-benzimidazole compound and thiosemicarbazide as raw materials, carrying out a reflux reaction to obtain 2-substituted-N-[5-(2-amino-1,3,4-thiadiazole)-methylene]-benzimidazole; then with 2-substituted-N-[5-(2-amino-1,3,4-thiadiazole)-methylene]-benzimidazole, aromatic aldehyde and p-toluenesulfonic acid as raw materials, carrying out a solid-phase reaction, and thus obtaining 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole. The preparation method has the advantages of simple reaction process, low equipment requirements, simple operation, relatively high target product yield, and small environmental pollution, and the prepared 2-substituted-N-[5-(2-(N-aryl methylene)amino-1,3,4-thiadiazole)-methylene]-benzimidazole can be applied in preparation of drugs inhibiting escherichia coli.
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Paragraph 0093
(2017/08/25)
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