6 research outputs found
Empirical and Theoretical Insights into the Structural Features and Host–Guest Chemistry of M<sub>8</sub>L<sub>4</sub> Tube Architectures
We
demonstrate a general method for the construction of M<sub>8</sub>L<sub>4</sub> tubular complexes via subcomponent self-assembly, starting
from Cu<sup>I</sup> or Ag<sup>I</sup> precursors together with suitable
elongated tetraamine and 2-formylpyridine subcomponents.
The tubular architectures were often observed as equilibrium mixtures
of diastereomers having two different point symmetries (<i>D</i><sub>2d</sub> or <i>D</i><sub>2</sub> ⇄ <i>D</i><sub>4</sub>) in solution. The equilibria between diastereomers
were influenced through variation in ligand length, substituents,
metal ion identity, counteranion, and temperature. In the presence
of dicyanoaurateÂ(I) and Au<sup>I</sup>, the <i>D</i><sub>4</sub>-symmetric hosts were able to bind linear AuÂ(AuÂ(CN)<sub>2</sub>)<sub>2</sub><sup>–</sup> (with two different configurations)
as the best-fitting guest. Substitution of dicyanoargentateÂ(I) for
dicyanoaurateÂ(I) resulted in the formation of AgÂ(AuÂ(CN)<sub>2</sub>)<sub>2</sub><sup>–</sup> as the optimal guest through transmetalation.
Density functional theory was employed to elucidate the host–guest
chemistries of the tubes
Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis
The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells and enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. This study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease
Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis.
The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells and enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. This study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease