RESUMO
Nucleobase modified neamines with a lysine as the linker (NbK-neamines) were synthesized and their binding toward hairpin RNAs derived from HIV-1 activator region were studied. NbK-neamines were bind those RNAs with micro molar level of binding affinities and compete with corresponding activator peptide for TAR RNA, but not for RRE RNA. GbK-neamine denotes the highest binding affinity with TAR RNA, three to five times higher than other three NbK-neamines. GbK-neamine could be a candidate of potential inhibitor for TAR-Tat.
Assuntos
Framicetina/química , Framicetina/farmacologia , Repetição Terminal Longa de HIV/efeitos dos fármacos , HIV-1/química , HIV-1/genética , Lisina/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Adenina/química , Citosina/química , Framicetina/síntese química , Guanina/química , Estrutura Molecular , Relação Estrutura-Atividade , Timina/químicaRESUMO
Twenty neamine derivatives having a nucleobase, adenine, cytosine, guanine or thimine with a lysine or an argine as a linker and, also, without linker were synthesized and their binding specificity for HIV TAR RNA was studied. Any nucleobase modification on neamine enhanced their binding affinities for TAR RNA. The binding affinity of neamine derivatives having a nucleobase at the closer position to neamine does not depend on the base, but having farther position has shown base specificity for TAR binding.
Assuntos
Aminoglicosídeos/química , Framicetina/química , Repetição Terminal Longa de HIV , RNA Viral/química , Purinas/química , Pirimidinas/químicaRESUMO
An outbreak of acute gastroenteritis consisting of 57 cases occurred in a mental health care facility in Takasaki city, Japan during 6th February and 27th March 2002. A total of 18 fecal specimens collected from 17 residents and one member of the medical staff during this outbreak were tested for the presence of viral enteropathogens by RT-PCR and latex agglutination. Group A rotavirus and sapovirus were detected in 5 out of 18 fecal specimens (55.6%). To our knowledge, this is the first finding of an outbreak of gastroenteritis associated with co-circulation of different kinds of viruses such as group A rotavirus and sapovirus. All of group A rotaviruses were typed further as P[4]G2 strains. Both rotavirus and sapovirus were subjected to molecular analysis by sequencing. It was noteworthy that all rotaviruses and sapoviruses had high homologies, respectively, to each other and sapoviruses presented a potential novel sapovirus genogroup I (GI) genotype, which was obviously different from any GI genotypes (GI-a, b, c, and d). The outbreak associated with these viruses spread gradually from dormitory to dormitory, suggesting a spread by person-to-person contact, although investigation on the route of transmission of the outbreak is lacking. The findings confirm the presence of group A rotavirus and sapovirus are important in acute gastroenteritis among adults in Japan.