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41.
Gaubert G Gosselin G Eriksson S Vita A Maury G 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):837-840
2'-Deoxy-beta-L-5-azacytidine(L-Decitabine), beta-L-5-azacytidine, and derivatives were stereospecifically prepared starting from L-ribose or L-xylose. D- and L-enantiomers of 2'-deoxy-beta-5-azacytidine were weak substrates of human recombinant deoxycytidine kinase (dCK), whereas both enantiomers of beta-5-azacytidine or the L-xylo-analogues were not substrates of the enzyme. None of the reported derivatives of beta-L-5-azacytidine was a substrate of human recombinant cytidine deaminase (CDA). 相似文献
42.
Salvetti R Pregnolato M Verri A Focher F Spadari S Marchand A Mathé C Gosselin G 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):1123-1125
Recently, beta-L-nucleoside analogues have emerged as a new class of sugar modified nucleosides with potential antiviral and/or antitumoral activity. As a part of our ongoing research on this topic, we decided to synthesize 5-CF3-beta-L-dUrd (7), the hitherto unknown L-enantiomer of Trifluridine, an antiherpetic drug approved by FDA but only used in topical applications due to concomitant cytotoxicity. 5-CF3-beta-L-dUrd (7) as well as some other related L-nucleoside derivatives were stereospecifically prepared and tested in vitro against viral (HSV-1 and HSV-2) and human thymidine kinases (TK). 相似文献
43.
Bryant ML Bridges EG Placidi L Faraj A Loi AG Pierra C Dukhan D Gosselin G Imbach JL Hernandez B Juodawlkis A Tennant B Korba B Cote P Cretton-Scott E Schinazi RF Sommadossi JP 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):597-607
A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a hydroxyl group in the 3'-position (3'-OH) of the beta-L-2'-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. Replacement of the 3'-OH broadens activity to other viruses. Substitution in the base decreases antiviral potency and selectivity. Human DNA polymerases and mitochondrial function are not effected. Plasma viremia is reduced up to 8 logs in a woodchuck model of chronic HBV infection. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection. 相似文献
44.
Gosselin I Zhou Y Bousquet J Isabel N 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,104(6-7):987-997
We have constructed linkage maps for two parents of white spruce [ Picea glauca (Moench) Voss]. Haploid megagametophytes from 92 and 96 seeds of parents M2 and 80132, respectively, were analysed with RAPD, SCAR and ESTP markers. Fragments segregating in a 1:1 Mendelian ratio were classified and mapped using MAPMAKER, GMENDEL and JOINMAP. For M2, the analysis with JOINMAP resulted in 165 loci (152 RAPDs, 3 SCARs and 10 ESTPs) mapping to 23 linkage groups and covering 2,059.4 cM(Kosambi function, K). For 80132, the analysis resulted in 144 loci (137 RAPDs, 1 SCAR and 7 ESTPs) mapping to 19 linkage groups and covering 2,007.7 cM(K). The maps covered 87 and 73% of the entire genome of parents M2 and 80132, respectively. Similar results were obtained with MAPMAKER and GMENDEL. A comparison was made between the two individual maps and 16 loci were shared between the two maps. 相似文献
45.
Walsh MC Banas JA Mudzinski SP Preissler MT Graziano RF Gosselin EJ 《Biomolecular engineering》2003,20(1):21-33
The professional antigen presenting cell (APC) plays an essential role in the initiation and propagation of the acquired immune response. Thus, much work has been done in designing strategies that target vaccine antigen (Ag) to APC. Utilizing recombinant DNA technology, we have created a unique two-component system that delivers biotinylated Ag to the Fc gamma receptor type I (FcgammaRI) on APC. Our studies demonstrate that we can successfully engineer FcgammaRI-specific targeting element proteins that simultaneously bind both biotin and recognize FcgammaRI. Additionally, we are able to engineer biotinylated Ag, which form functional elements when adsorbed onto latex microspheres. Furthermore, the targeting and functional element components bind to each other and successfully form two-component immunogens. T-cell activation in response to targeted Ag-laden microspheres is 10- to 100-fold greater than the response to the non-targeted Ag-laden microspheres. This enhancement is 100- to 1000-fold greater than the responses generated to soluble Ag. Thus, our results suggest that specific targeting of Ag-laden microspheres to FcgammaRI may significantly enhance the adjuvant properties of microparticulate delivery systems. Further development of this system may help to elucidate the mechanisms involved in generating enhanced responses to APC-targeted vaccines and significantly advance vaccine technology. 相似文献
46.
3'-C-Trifloromethyl-beta-D-ribonucleoside derivatives bearing the five naturally occurring nucleic acid bases have been synthesized. All these derivatives were prepared by glycosylation reactions of purine and pyrimidine bases with a suitable peracylated 3-C-trifluoromethyl ribofuranose precursor. After deprotection, the resulting title nucleoside analogues were tested for their inhibitory properties against the replication of HIV, HBV and several RNA viruses. However, none of these compounds showed significant antiviral activity. 相似文献
47.
Colacino E Sindona G Gosselin G Mathé C 《Nucleosides, nucleotides & nucleic acids》2003,22(11):2013-2026
In this article, we describe the synthesis of 5-nitro-1-(2-deoxy-alpha-D-erythro-pentofuranosyl)cytosine (4alpha), 5-nitro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)cytosine (4beta), 5-amino-1-(2-deoxy-alpha-D-erythro-pentofuranosyl)cytosine (5alpha), 5-nitro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)cytosine (5beta), 5-nitro-1-(2,3-dideoxy-beta-D-ribofuranosyl)uracil (6beta), 5-amino-1-(2,3-dideoxy-alpha,beta-D-ribofuranosyl)uracil (7), 5-nitro-1-(2,3-dideoxy-alpha,beta-D-ribofuranosyl)cytosine (8) and 5-amino-1-(2,3-dideoxy-beta-D-ribofuranosyl)cytosine (9beta). The prepared compounds were tested for their activity against HIV and HBV viruses, but they did not show significant activity. 相似文献
48.
Benzaria S Pierra C Bardiot D Cretton-Scott E Bridges EG Zhou XJ Standring D Gosselin G 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1003-1006
In order to improve the oral bioavailability of LdC, valinyl esters were prepared as prodrugs. We report here the syntheses of the 3'-mono-, 5'-mono, and 3',5'-di-O-valinyl esters of LdC. The comparison of their ease of synthesis, their physicochemical properties, as well as their pharmacokinetic parameters in cynomologus monkeys has revealed 3'-mono-O-valinyl derivative as the most promising of the studied prodrugs. This compound is being developed as a new anti-HBV agent. 相似文献
49.
Jochum A Schlienger N Gosselin G Imbach JL Aubertin AM Périgaud C 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):899-901
The synthesis and the study of two phosphorothiolate derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-pivaloyl-2-thioethyl (tBuSATE) group and glucosyl residues associated to the phosphorus atom by a 2-oxyethyl link, are reported. These derivatives could be considered as prototypes of a new series of nucleotide prodrugs (pronucleotides). 相似文献
50.
3'-Deoxy-beta-L-erythro- (3), 3'-deoxy-beta-L-threo- (6), 2'-fluoro- (7) and 2'-azido-2',3'-dideoxy-beta-L-erythro- (10) pentofuranonucleoside derivatives of thymine have been synthesized and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of thymine with a suitable peracylated 3-deoxy-L-erythro-pentofuranose sugar (1), followed by appropriate chemical modifications. The prepared compounds were tested for their activity against HIV, but they did not show an antiviral effect. 相似文献