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J Med Chem ; 34(7): 2195-202, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2066992


A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).

Antineoplásicos/síntese química , Antivirais/síntese química , Didesoxinucleosídeos/síntese química , Hidrocarbonetos Fluorados/síntese química , Animais , Antineoplásicos/farmacologia , Antivirais/farmacologia , Linhagem Celular , Fenômenos Químicos , Química , Didesoxinucleosídeos/farmacologia , Humanos , Hidrocarbonetos Fluorados/farmacologia , Leucemia L1210/tratamento farmacológico , Testes de Sensibilidade Microbiana , Coelhos , Relação Estrutura-Atividade , Células Tumorais Cultivadas/efeitos dos fármacos
Nucleic Acids Symp Ser ; (24): 67-70, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1841383


Rabbit antibodies to 2',5'-linked triadenylate were prepared by immunization with (2',5')A3 conjugated via the 2'3'-levulinic group, (2'5')A3-Lev, to BSA. New radioimmunoassay for (2',5')oligoadenylates was developed using 125I thyrosine labeled derivative of (2',5')A3-Lev. Reactivity of antibodies with phosphorothioate and seco analogs of oligoadenylates was studied. It was found that (i) stereospecific substitution of the diastereotopic oxygens with sulfur in the internucleotide phosphodiester linkages changes the immunoreactivity of such analogs; (ii) the seco analogs of oligoadenylates display in some cases a rather high reactivity.

Nucleotídeos de Adenina/imunologia , Antivirais/imunologia , Oligorribonucleotídeos/imunologia , Animais , Especificidade de Anticorpos , Antivirais/síntese química , Reações Cruzadas , Coelhos/imunologia , Relação Estrutura-Atividade
Appl Microbiol Biotechnol ; 32(6): 658-61, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1367439


Synthesis of 9-(beta-D-arabinofuranosyl)guanine (ara-G) from 1-(beta-D-arabinofuranosyl)cytosine (ara-C) and guanine, guanosine or 2'-deoxyguanosine (dG) by glutaraldehyde-treated Escherichia coli BM-11 cells is described. It is shown that the concentration of phosphate ions, molar ratio of substrates and pH of the reaction medium are factors affecting product yield. Under optimum conditions ara-G was produced in the reaction mixture in a yield of 63%-65% based on dG as the best source of guanine base. The yield of isolated ara-G was 48%-53%.

Arabinonucleosídeos/biossíntese , Escherichia coli/metabolismo , Arabinonucleosídeos/isolamento & purificação , Proteínas de Bactérias/metabolismo , Citarabina/metabolismo , Citosina Desaminase , Glutaral , Guanina/metabolismo , Nucleotídeos de Guanina/metabolismo , Nucleosídeo Desaminases/metabolismo , Purina-Núcleosídeo Fosforilase/metabolismo , Uridina Fosforilase/metabolismo
FEBS Lett ; 250(2): 139-41, 1989 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-2473915


3'-Fluoro-3'-deoxy-uridine, -cytidine, -adenosine and -guanosine have been synthesized by glycosylation of the corresponding silylated bases with 1-O-acetyl-2,5-di-O-benzoyl-3-fluoro-3-deoxy-D-ribofuranose in the presence of Friedel-Crafts catalysts and were converted to the 5'-triphosphates, NTP(3'-F). It was shown that NTP(3'-F) are terminators of RNA synthesis catalyzed by DNA-dependent RNA polymerase from E. coli and may thus serve as tools for DNA sequencing.

Desoxirribonucleotídeos/síntese química , RNA/biossíntese , Sequência de Bases , Catálise , Fenômenos Químicos , Química , DNA Polimerase Dirigida por DNA/metabolismo , Desoxirribonucleotídeos/farmacologia , Eletroforese em Gel de Ágar , Escherichia coli/enzimologia , Dados de Sequência Molecular , RNA/antagonistas & inibidores
FEBS Lett ; 183(2): 275-8, 1985 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-2580738


It is shown that dNTP(3'F) are terminators of DNA synthesis and may serve as very effective tools for DNA sequencing with E.coli DNA polymerase I and AMV reverse transcriptase. The dNTP(3'F) are found to be chain terminator substrates for calf thymus terminal deoxyribonucleotidyl transferase but not for calf thymus DNA polymerase alpha. The optimal dNTP(3'F) concentration for DNA sequencing by DNA polymerase I is found to be an order of magnitude lower than that of ddNTPs. dNTP(3'F) produce a more clear sequence pattern than do ddNTPs.

Replicação do DNA/efeitos dos fármacos , Desoxirribonucleotídeos/farmacologia , Flúor/farmacologia , Animais , Sequência de Bases , Bovinos , DNA Nucleotidilexotransferase/metabolismo , DNA Polimerase I/metabolismo , Escherichia coli , DNA Polimerase Dirigida por RNA/metabolismo