RESUMO
A,D-substituted cyclodextrin (CDX) substituted on their primary rim side are ideal scaffolds for the macromolecular assembly and formation of templated structures. Their substitution can be achieved through various reactions. However, the use of the well-known Huisgen reaction in this context is under-reported. We present here results of the synthesis of model conjugates formed between CDX and representative peptides by click chemistry. Notably, bis-conjugation of peptides onto a unique scaffold promotes α-helix formation. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Assuntos
Química Click/métodos , Ciclodextrinas/química , Peptídeos/química , Alcinos/química , Sequência de Aminoácidos , Azidas/química , Cobre/química , Modelos Moleculares , Conformação Proteica em alfa-HéliceRESUMO
The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either ß- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1 complexes were observed, with 2:1 host:guest complexes observed in just 6 out of 38 host:guest combinations. It is shown that these higher-order complexes were observed only in the case of small (or no) electronically withdrawing substituents, and were much less likely in the case of the larger γ-cyclodextrin host. The size and electronic properties of the substituents involved shows that both steric and electronic factors must be taken into account in predicting which cyclodextrin host:guest stoichiometries will be stable enough to form (or once formed, be robust enough to be observed in the ESI-MS experiments). It is clear that the prediction of host-guest stoichiometry for a specific host-guest pair is complicated, and involves a subtle interplay of both electronic and steric factors. However, there are definite trends, which can be used to help predict host:guest stoichiometry for a given host-guest pair.
Assuntos
Naftoquinonas/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Modelos Moleculares , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution (1)H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution (1)H- and (13)C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10(-5) M, respectively), indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10(-3) M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic.