RESUMO
Quinoxapeptin A and B are novel chromodepsipeptides which were isolated from a nocardioform actinomycete with indeterminant morphology. Quinoxapeptins A and B are potent inhibitors of HIV-1 and HIV-2 reverse transcriptase and almost equally active against two single mutants forms as well as a double mutant form of HIV-1 reverse transcriptase. Quinoxapeptin A and B are specific inhibitors of HIV-1 and HIV-2 reverse transcriptase because they did not inhibit human DNA polymerase alpha, beta, gamma and delta. Quinoxapeptin A and B are structurally similar to luzopeptin A which was also active against HIV-1 and HIV-2 reverse transcriptase.
Assuntos
HIV-1/enzimologia , HIV-2/enzimologia , Peptídeos Cíclicos/metabolismo , Peptídeos Cíclicos/farmacologia , Quinoxalinas/metabolismo , Quinoxalinas/farmacologia , DNA Polimerase Dirigida por RNA/metabolismo , Inibidores da Transcriptase Reversa/metabolismo , Inibidores da Transcriptase Reversa/farmacologia , Actinomycetales/classificação , Actinomycetales/metabolismo , Transcriptase Reversa do HIV , HIV-1/genética , Humanos , Hidroxiquinolinas/química , Hidroxiquinolinas/farmacologia , Técnicas In Vitro , Cinética , Estrutura Molecular , Mutação , Inibidores da Síntese de Ácido Nucleico , Peptídeos Cíclicos/química , Quinoxalinas/química , DNA Polimerase Dirigida por RNA/genética , Inibidores da Transcriptase Reversa/químicaRESUMO
Chaetomellic acids A and B, isolated from Chaetomella acutiseta, are specific inhibitors of farnesyl-protein transferase that do not inhibit geranylgeranyl transferase type 1 or squalene synthase. Chaetomellic acids A and B are reversible inhibitors, resemble farnesyl diphosphate and probably inhibit FPTase by substituting for farnesyl diphosphate. Chaetomellic acid production appears to be widespread within the genus Chaetomella.
Assuntos
Alquil e Aril Transferases , Maleatos/metabolismo , Fungos Mitospóricos/metabolismo , Transferases/antagonistas & inibidores , Fermentação , Maleatos/isolamento & purificação , Maleatos/farmacologiaRESUMO
Actinoplanic acids A and B are macrocyclic polycarboxylic acids that are potent reversible inhibitors of farnesyl-protein transferase. Actinoplanic acids A and B were isolated from Actinoplanes sp. MA 7066 while actinoplanic acid B was isolated from both MA 7066 and Streptomyces sp. MA 7099. Actinoplanic acids A and B are competitive with respect to farnesyl diphosphate and are selective inhibitors of farnesyl-protein transferase because they do not inhibit geranylgeranyl-protein transferase type 1 or squalene synthase. MA 7066 is believed to be a novel species of actinomycetes while MA 7099 is believed to be a novel strain of Streptomyces violaceusniger on the basis of morphological, biochemical and chemotaxonomic characteristics as well as its production of actinoplanic acids.