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.
