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Natalia Dyatkina Dniitry Semizarov Lyubov Victorova Alexander Krayevsky Fritz Theil Martin von Janta-Lipinski 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):723-726
Abstract A method was developed for synthesis of the four stereoisomeric enantiomerically pure 5′-nor carbocyclic nucleosides 4b, ent-4b, 10 and ent-10 starting from the common enantiomerically pure allylic monoacetate 1. Nucleoside analogues were converted to the corresponding triphosphate derivatives 6, ent-6, 12, and ent-12. The substrate properties of the latters towards different DNA polymerases were evaluated. 相似文献
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Sharkin Yu. A. Semizarov D. G. Viktorova L. S. Kukhanova M. K. 《Russian Journal of Bioorganic Chemistry》2001,27(5):340-348
Several modified nucleoside 5"-triphosphates containing adenine-mimicking pyrimidine derivatives as an aglycone were synthesized. The study of substrate properties of these compounds towards DNA-synthesizing enzymes showed their ability of being incorporated into the growing DNA chain in place of dATP. 相似文献
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Several modified nucleoside 5'-triphosphates were synthesized containing adenine-mimicking pyrimidine derivatives as an aglycone. The study of substrate properties of these compounds towards DNA-synthesizing enzymes showed their ability of being incorporated into the growing DNA chain in place of dATP. 相似文献
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Alexander A. Krayevsky Natalya B. Dyatkina Dmitry G. Semizarov Liubov S. Victorova Elena A. Shirokova Fritz Theil 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):863-864
Abstract Theoretical and experimental analysis of interaction of modified D- and L- dNTP as substrates for template-dependent and template-independent DNA polymerases was performed. It is shown that if the modified nucleoside 5′-triphosphates do not contain a substituent in position 3′ DNA chains can be extended by both strereoisomeric series with the same kinetic parameters. But the presence of even a 3′- hydroxy group in L-dNTP prevents their incorporation into the DNA chain. 相似文献
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Olejniczak ET Van Sant C Anderson MG Wang G Tahir SK Sauter G Lesniewski R Semizarov D 《Molecular cancer research : MCR》2007,5(4):331-339
Cancer is a highly heterogeneous disease in terms of the genetic profile and the response to therapeutics. An early identification of a genomic marker in drug discovery may help select patients that would respond to treatment in clinical trials. Here we suggest coupling compound screening with comparative genomic hybridization analysis of the model systems for early discovery of genomic biomarkers. A Bcl-2 antagonist, ABT-737, has recently been discovered and shown to induce regression of solid tumors, but its activity is limited to a fraction of small-cell lung carcinoma (SCLC) models tested. We used comparative genomic hybridization on high-density single-nucleotide polymorphism genotyping arrays to carry out a genome-wide analysis of 23 SCLC cell lines sensitive and resistant to ABT-737. The screen revealed a number of novel recurrent gene copy number abnormalities, which were also found in an independent data set of 19 SCLC tumors and confirmed by real-time quantitative PCR. A previously unknown amplification was identified on 18q and associated with the sensitivity of SCLC cell lines to ABT-737 and another Bcl-2 antagonist. The region of gain contains Bcl-2 and NOXA, two apoptosis-related genes. Expression microarray profiling showed that the genes residing in the amplified region of 18q are also overexpressed in the sensitive lines relative to the resistant lines. Fluorescence in situ hybridization analysis of tumors revealed that Bcl-2 gain is a frequent event in SCLC. Our findings suggest that 18q21-23 copy number will be a clinically relevant predictor for sensitivity of SCLC to Bcl-2 family inhibitors. The 18q21-23 genomic marker may have a broader application in cancer because Bcl-2 is associated with apoptosis evasion and chemoresistance. 相似文献
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A A Krayevsky N B Dyatkina D G Semizarov L S Victorova E A Shirokova F Theil M J Von Janta Lipinski G Gosselin J L Imbach 《Nucleosides & nucleotides》1999,18(4-5):863-864
Theoretical and experimental analysis of interaction of modified D- and L- dNTP as substrates for template-dependent and template-independent DNA polymerases was performed. It is shown that if the modified nucleoside 5'-triphosphates do not contain a substituent in position 3' DNA chains can be extended by both strereoisomeric series with the same kinetic parameters. But the presence of even a 3'-hydroxy group in L-dNTP prevents their incorporation into the DNA chain. 相似文献
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