RESUMO
Zinc fingers have rarely been regarded as drug targets. On the contrary, the zinc-binding site of enzymes has often been considered a target of inhibitors. We previously developed a dithiol compound called SN-1 that binds to the zinc finger protein tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppresses downstream nuclear factor-κB (NF-κB) signaling. To determine the minimal structure requirements of TRAF6 inhibitors based on SN-1, NF-κB inhibitory activity and cytotoxicity of its derivatives including new compounds were examined. SN-2, an oxidative type of prodrug of SN-1 with 2-nitrophenylthio groups via disulfide, has the minimum structure for an inhibitor of TRAF6, as seen with cellular experiments. The importance of two side chains with a thiol group was shown with molecular modelling. This study may lead to development of selective TRAF6 inhibitors in the near future.
Assuntos
Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Dedos de Zinco/genética , Humanos , Estrutura MolecularRESUMO
The incorporation of neutral [70]fullerenes (C70) led to bicelle formation in a relatively low lipid concentration range from neutral lipid mixtures (DMPC/DHPC). Furthermore, C70 addition resulted in the formation of large bicelles with a radius of ca. 100 nm, in contrast to C70-free bicelles that were formed from anionic lipid mixtures (DMPC/DHPC/DMPG). The stabilization of these bicelles was attributed to C70 incorporation into the membranes.
Assuntos
Fulerenos/química , Fosfolipídeos/análise , Fosfolipídeos/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
To obtain direct evidence for the fullerene-exchange reactions from the γ-cyclodextrin cavities to the lipid membranes following the addition of a C70·Î³-cyclodextrin complex, we monitored the dynamic behaviours of the giant unilamellar vesicles. A number of C70 aggregates generated in the lipid membranes moved about vigorously.
Assuntos
Fulerenos/química , Lipossomas Unilamelares/química , gama-Ciclodextrinas/química , Lipídeos de Membrana/química , Fosfatidilcolinas/químicaRESUMO
Cyclodextrins (CDxs) have been selectively deuterated using a Ru/C-catalyzed H-D exchange reaction in D2O. The structures of the deuterated CDxs barely changed and their (1)H NMR spectra became very simple, which made it possible for the deuterated CDxs to be applied to the analysis of CDx complexes. Furthermore, the deuterated CDxs allowed for the existence of the equilibrium between free and complexed CDx to be confirmed, even at rt.