RESUMO
[structure--see text] Bioassay-guided fractionation of extracts of the Palauan ascidian Didemnum guttatum led to the isolation of cyclodidemniserinol trisulfate (1) as an inhibitor of HIV-1 integrase, which is an attractive target for anti-retroviral chemotherapy. The structure of cyclodidemniserinol trisulfate (1), the stereochemistry of which was only partially determined, was elucidated by interpretation of NMR and mass spectral data.
Assuntos
Inibidores de Integrase de HIV/química , Urocordados/química , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/metabolismo , Fatores Biológicos , Citomegalovirus/enzimologia , DNA Topoisomerases Tipo I/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/isolamento & purificação , Inibidores de Integrase de HIV/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Lipídeos/isolamento & purificação , Biologia Marinha , Espectrometria de Massas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Propanolaminas , Propilenoglicóis/química , Propilenoglicóis/isolamento & purificação , Propilenoglicóis/metabolismo , Sulfatos/química , Sulfatos/isolamento & purificação , Sulfatos/metabolismo , Inibidores da Topoisomerase IRESUMO
A collection of Lyngbya majuscula from Palau contained the peptides dolastatin 3 (1), homodolastatin 3 (2), and kororamide (3), together with aplysiatoxin (4), debromoaplysiatoxin (5), and oscillatoxin A (6). The structures of the new peptides homodolastatin 3 (2) and kororamide (3) were determined by interpretation of spectroscopic data and chemical degradation.
Assuntos
Depsipeptídeos , Inibidores de Integrase de HIV/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Aminoácidos/análise , Cromatografia Gasosa-Espectrometria de Massas , Inibidores de Integrase de HIV/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Palau , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
The three-dimensional structure of conotoxin psi-PIIIE, a 24-amino acid peptide from Conus purpurascens, has been solved using two-dimensional (2D) 1H NMR spectroscopy. Conotoxin psi-PIIIE contains the same disulfide bonding pattern as the mu-conotoxins, which target skeletal muscle sodium channels, but has been shown to antagonize the acetylcholine gated cation channel through a noncompetitive mechanism. Structural information was obtained by the analysis of a series of 2D NOESY spectra as well as measurement of coupling constants from 1D 1H and PE-COSY NMR experiments. Molecular modeling calculations included the use of the distance geometry (DG) algorithm, simulated annealing techniques, and the restrained molecular dynamics method. The resulting structures are considerably similar to the previously published structures for the mu-conotoxins GIIIA and GIIIB, despite the lack of sequence conservation between conotoxin psi-PIIIE and the mu-conotoxins. The structure consists of a series of tight turns, each turn occurring in the position analogous to those of turns described in mu-GIIIA and mu-GIIIB. This suggests the disulfide bonding pattern is able to largely direct the structure of the peptides, creating a stable structural motif which allows extensive sequence substitution of non-cystine residues.
Assuntos
Venenos de Moluscos/química , Antagonistas Nicotínicos/química , Peptídeos/química , Bloqueadores dos Canais de Sódio , ômega-Conotoxinas , Sequência de Aminoácidos , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Venenos de Moluscos/farmacologia , Antagonistas Nicotínicos/farmacologia , Peptídeos/farmacologia , Estrutura Secundária de Proteína , SoluçõesRESUMO
The new compound 1,3-dimethylisoguanine has been isolated and characterized from the Bermudian sponge Amphimedon viridis. Chemical conversion of the natural product to theophylline and 2D NMR methods were used to determine the position of the methyl groups on the purine ring. Analysis of the mass spectral fragmentation pattern allowed assignment of the purine ring as isoguanine.
Assuntos
Antineoplásicos/isolamento & purificação , Guanina/análogos & derivados , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Guanina/química , Guanina/isolamento & purificação , Guanina/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Células Tumorais CultivadasRESUMO
Two new 5'-deoxypyrrolo[2,3-d]pyrimidine (7-deazapurine) nucleosides, 5'-deoxytubercidin and 5'-deoxy-3-bromotubercidin, were identified from the ascidian Didemnum voeltzkowi. Two known anomers of 5'-deoxy-3-iodotubercidin were also purified from the extract. Assignments were made on the basis of 1H and 13C chemical shifts as well as HPLC-MS experiments.
