RESUMO
Novel thymidine dimers containing hydroxamate linkages were synthesized, incorporated into oligonucleotide sequences and studied their hybridization properties against complementary DNA and RNA targets.
Assuntos
Ácidos Hidroxâmicos/química , Oligonucleotídeos/química , Nucleotídeos de Pirimidina/química , DNA/química , Ácidos Hidroxâmicos/síntese química , Hibridização de Ácido Nucleico , Oligonucleotídeos/síntese química , Dímeros de Pirimidina/síntese química , Dímeros de Pirimidina/química , Nucleotídeos de Pirimidina/síntese química , RNA/química , Timidina/análogos & derivadosRESUMO
A new synthesis of tiazofurin is described from 2,3-O-isopropylidene-5-O-benzoyl-beta-D-ribofuranosyl cyanide.
Assuntos
Antimetabólitos Antineoplásicos/síntese química , Ribavirina/síntese química , Ribavirina/análogos & derivadosRESUMO
A series of 1,2,4-triazole L-nucleosides were synthesized and evaluated for their ability to stimulate type 1 cytokine production by activated human T cells in direct comparison to the known active agent ribavirin. Among the compounds prepared, 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamide (5, ICN 17261) was found to be the most uniformly potent compound. Conversion of the 3-carboxamide group of 5 to a carboxamidine functionality resulted in 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (10), which induced cytokine levels comparable to 5 for two of the three type 1 cytokines examined. Modification of the carbohydrate moiety of 5 provided compounds of reduced activity. Significantly, ICN 17261 offers interesting immunomodulatory potential for the treatment of diseases where type 1 cytokines play an important role.
Assuntos
Adjuvantes Imunológicos/síntese química , Citocinas/metabolismo , Nucleosídeos/síntese química , Ribavirina/síntese química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas In Vitro , Interferon gama/metabolismo , Interleucina-2/metabolismo , Nucleosídeos/química , Nucleosídeos/farmacologia , Ribavirina/química , Ribavirina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Novel serine derivative of thymine was prepared and incorporated into oligonucleotides. These modified oligonucleotides were studied for their binding affinity with complementary DNA/RNA.
