Nucleosides & nucleotides最新文献_第4页

Synthesis and antiviral activity of 1,5- and 1,3-dialkyl-1,2,4-triazole C-nucleosides derived from 1-(chloroalkyl)-1-aza-2-azoniaallene salts. 由1-(氯烷基)-1-氮杂-2-氮杂烯盐衍生的1,5-和1,3-二烷基-1,2,4-三唑c -核苷的合成及抗病毒活性

Nucleosides & nucleotides Pub Date : 1999-09-01 DOI: 10.1080/07328319908044859

Y A al-Soud, W A al-Masoudi, R A el-Halawa, N al-Masoudi

引用次数: 15

Evaluation of different types of end-capping modifications on the stability of oligonucleotides toward 3'- and 5'-exonucleases. 不同类型的端盖修饰对寡核苷酸对3′-和5′-外切酶稳定性的影响。

Nucleosides & nucleotides Pub Date : 1999-09-01 DOI: 10.1080/07328319908044864

D Pandolfi, F Rauzi, M L Capobianco

引用次数: 19

Substrate/inhibitor properties of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2) towards the sugar moiety of nucleosides, including O'-alkyl analogues. 人脱氧胞苷激酶(dCK)和胸苷激酶(TK1和TK2)对核苷(包括O'-烷基类似物)糖片段的底物/抑制剂特性

Nucleosides & nucleotides Pub Date : 1999-08-01 DOI: 10.1080/07328319908044850

B Kierdaszuk, K Krawiec, Z Kazimierczuk, U Jacobsson, N G Johansson, B Munch-Petersen, S Eriksson, D Shugar

{"title":"Substrate/inhibitor properties of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2) towards the sugar moiety of nucleosides, including O'-alkyl analogues.","authors":"B Kierdaszuk, K Krawiec, Z Kazimierczuk, U Jacobsson, N G Johansson, B Munch-Petersen, S Eriksson, D Shugar","doi":"10.1080/07328319908044850","DOIUrl":"https://doi.org/10.1080/07328319908044850","url":null,"abstract":"Nucleoside analogues with modified sugar moieties have been examined for their substrate/inhibitor specificities towards highly purified deoxycytidine kinase (dCK) and thymidine kinases (tetrameric high-affinity form of TK1, and TK2) from human leukemic spleen. In particular, the analogues included the mono- and di-O'-methyl derivatives of dC, dU and dA, syntheses of which are described. In general, purine nucleosides with modified sugar rings were feebler substrates than the corresponding cytosine analogues. Sugar-modified analogues of dU were also relatively poor substrates of TK1 and TK2, but were reasonably good inhibitors, with generally lower Ki values vs TK2 than TK1. An excellent discriminator between TK1 and TK2 was 3'-hexanoylamino-2',3'-dideoxythymidine, with a Ki of approximately 600 microM for TK1 and approximately 0.1 microM for TK2. 3'-OMe-dC was a superior inhibitor of dCK to its 5'-O-methyl congener, consistent with possible participation of the oxygen of the (3')-OH or (3')-OMe as proton acceptor in hydrogen bonding with the enzyme. Surprisingly alpha-dT was a good substrate of both TK1 and TK2, with Ki values of 120 and 30 microM for TK1 and TK2, respectively; and a 3'-branched alpha-L-deoxycytidine analogue proved to be as good a substrate as its alpha-D-counterpart. Several 5'-substituted analogues of dC were good non-substrate inhibitors of dCK and, to a lesser extent, of TK2. Finally, some ribonucleosides are substrates of the foregoing enzymes; in particular C is a good substrate of dCK, and 2'-OMe-C is an even better substrate than dC.","PeriodicalId":19222,"journal":{"name":"Nucleosides & nucleotides","volume":"18 8","pages":"1883-903"},"PeriodicalIF":0.0,"publicationDate":"1999-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07328319908044850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21341914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

Synthesis and biophysical studies of modified oligonucleotides containing acyclic amino alcohol nucleoside analogs. 含无环氨基醇核苷类似物修饰寡核苷酸的合成及生物物理研究。

Nucleosides & nucleotides Pub Date : 1999-08-01 DOI: 10.1080/07328319908044847

K S Ramasamy, V Stoisavljevic

引用次数: 3

Synthesis and triplex forming properties of pyrimidine derivative containing extended functionality. 含扩展官能团嘧啶衍生物的合成及三络合性质。

Nucleosides & nucleotides Pub Date : 1999-08-01 DOI: 10.1080/07328319908044841

D A Gianolio, L W McLaughlin

引用次数: 6

Increased cytotoxicity and decreased in vivo toxicity of FdUMP[10] relative to 5-FU. 相对于5-FU, FdUMP的细胞毒性增加，体内毒性降低[10]。

Nucleosides & nucleotides Pub Date : 1999-08-01 DOI: 10.1080/07328319908044843

J Liu, A Skradis, C Kolar, J Kolath, J Anderson, T Lawson, J Talmadge, W H Gmeiner

{"title":"Increased cytotoxicity and decreased in vivo toxicity of FdUMP[10] relative to 5-FU.","authors":"J Liu, A Skradis, C Kolar, J Kolath, J Anderson, T Lawson, J Talmadge, W H Gmeiner","doi":"10.1080/07328319908044843","DOIUrl":"https://doi.org/10.1080/07328319908044843","url":null,"abstract":"The efficacy of treatment with 5-Fluorouracil (5-FU) is limited, in part, by its inefficient conversion to 5-Fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP). We present data indicating that FdUMP[10], designed as a pro-drug for intracellular release of FdUMP, is cytotoxic as a consequence of uptake of the multimeric form. FdUMP[10] is stable in cell culture medium, with more than one-half of the material persisting as multimers of at least six nucleotides after a 48 h incubation at 37 degrees C. FdUMP[10] is more than 400 times more cytotoxic than 5-FU towards human colorectal tumor cells (H630). FdUMP[10] also has decreased toxicity in vivo, with doses as high as 200 mg/kg/day (qdx3) administered to Balb/c mice without morbidity, compared to a maximum tolerated dose of 45 mg/kg/day for 5-FU using the same protocol. FdUMP[10] shows reduced sensitivity to OPRTase- and TK-mediated drug resistance, relative to 5-FU and FdU, respectively, and is much more cytotoxic than 5-FU towards cells that overexpress thymidylate synthase. Thus, FdUMP[10] is less susceptible to resistance mechanisms that limit the clinical utility of 5-FU. The increased cytotoxicity, decreased toxicity in vivo, and reduced sensitivity to drug resistance of FdUMP[10], relative to 5-FU, indicates multimeric FdUMP is potentially valuable as an anti-neoplastic agent, either as a single agent, or in combination with 5-FU.","PeriodicalId":19222,"journal":{"name":"Nucleosides & nucleotides","volume":"18 8","pages":"1789-802"},"PeriodicalIF":0.0,"publicationDate":"1999-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/07328319908044843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21341913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

A phosphate bound universal linker for DNA synthesis. 一种用于DNA合成的磷酸盐结合的通用连接体。

Nucleosides & nucleotides Pub Date : 1999-08-01 DOI: 10.1080/07328319908044845

M H Lyttle, D J Dick, D Hudson, R M Cook

引用次数: 14

Synthesis and anti-HIV activity of different novel nonclassical nucleosides. 不同新型非经典核苷的合成及抗hiv活性研究。

Nucleosides & nucleotides Pub Date : 1999-06-15 DOI: 10.1002/CHIN.199924235

G. Elgemeie, O. Mansour, N. Metwally