RESUMO
The MeOH extract of an Indonesia Eudistoma sp. ascidian contained 1,3,O(7)-trimethylisoxanthopterin (1), a novel pteridine. The purification of 1 was achieved through flash C(18) chromatography and cyano HPLC. The structure was determined primarily through the use of (1)H-(13)C and (1)H-(15)N HMBC measurements and comparison with data obtained for 1,3,7-trimethylguanine (2).
Assuntos
Guanina/isolamento & purificação , Pterinas/isolamento & purificação , Urocordados/química , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Guanina/análogos & derivados , Guanina/química , Guanina/farmacologia , Indonésia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pterinas/química , Pterinas/farmacologia , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierAssuntos
Antibacterianos/química , Aspergillus niger/química , Cicloexanos/química , Compostos de Epóxi/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , EstereoisomerismoRESUMO
kappa-Conotoxin PVIIA (kappa-PVIIA), a 27-amino acid peptide with three disulfide cross-links, isolated from the venom of Conus purpurascens, is the first conopeptide shown to inhibit the Shaker K(+) channel (Terlau, H., Shon, K., Grilley, M., Stocker, M., Stühmer, W., and Olivera, B. M. (1996) Nature 381, 148-151). Recently, two groups independently determined the solution structure for kappa-PVIIA using NMR; although the structures reported were similar, two mutually exclusive models for the interaction of the peptide with the Shaker channel were proposed. We carried out a structure/function analysis of kappa-PVIIA, with alanine substitutions for all amino acids postulated to be key residues by both groups. Our data are consistent with the critical dyad model developed by Ménez and co-workers (Dauplais, M., Lecoq, A., Song, J. , Cotton, J., Jamin, N., Gilquin, B., Roumestand, C., Vita, C., de Medeiros, C., Rowan, E. G., Harvey, A. L., and Ménez, A. (1997) J. Biol. Chem. 272, 4802-4809) for polypeptide antagonists of K(+) channels. In the case of kappa-PVIIA, Lys(7) and Phe(9) are essential for activity as predicted by Savarin et al. (Savarin, P., Guenneugues, M., Gilquin, B., Lamthanh, H., Gasparini, S., Zinn-Justin, S., and Ménez, A. (1998) Biochemistry 37, 5407-5416); these workers also correctly predicted an important role for Lys(25). Thus, although kappa-conotoxin PVIIA has no obvious sequence homology to polypeptide toxins from other venomous animals that interact with voltage-gated K(+) channels, there may be convergent functional features in diverse K(+) channel polypeptide antagonists.
Assuntos
Conotoxinas/química , Conotoxinas/farmacologia , Bloqueadores dos Canais de Potássio , Canais de Potássio/química , Alanina , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sítios de Ligação , Dissulfetos , Modelos Moleculares , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Peptídeos/farmacologia , Mutação Puntual , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , CaramujosRESUMO
The MeOH extract of an undescribed Eudistoma sp. ascidian was found to contain the known beta-carboline trypargine (3); the two novel trypargine derivatives trypargimine (4) and 1-carboxytrypargine (5); and 3',5'-dibromo-4'-methoxyphenethylamine (6). The structures of the novel trypargine derivatives were elucidated through the use of mass spectrometry and NMR. The trypargine isolated in this study was found to be nearly racemic in contrast to the previously described isolate which was chiroptically pure. Other previously described compounds detected in the MeOH extract include 4-hydroxyphenylacetamide, tryptamine, 1,3,7-trimethylguanine, and tetrahydropentoxyline (7).
