10 research outputs found
Crystallization and Interconversions of Vapor-Sensitive, Luminescent Polymorphs of [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>](AsF<sub>6</sub>) and [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>](PF<sub>6</sub>)
The remarkable, vapor-induced transformation of the yellow
polymorphs
of [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>]Â(AsF<sub>6</sub>) and [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>]Â(PF<sub>6</sub>) into the colorless forms are reported along with
related studies of the crystallization of these polymorphs. Although
the interconversion of these polymorphs is produced by vapor exposure, <i>molecules of the vapor are not incorporated into the crystals</i>. Thus, our observations may have broad implications regarding the
formation and persistence of other crystal polymorphs where issues
of stability and reproducibility of formation exist. Crystallographic
studies show that the colorless polymorphs, which display blue luminescence,
are isostructural and consist of linear chains of goldÂ(I) cations
that self-associate through aurophilic interactions. Significantly,
the yellow polymorph of [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>]Â(AsF<sub>6</sub>) is not isostructural with the yellow
polymorph of [(C<sub>6</sub>H<sub>11</sub>NC)<sub>2</sub>Au<sup>I</sup>]Â(PF<sub>6</sub>). Both yellow polymorphs exhibit green emission
and have the gold cations arranged into somewhat bent chains with
significantly closer Au···Au separations than are seen
in the colorless counterparts. Luminescence differences in these polymorphs
clearly enhance the ability to detect and monitor their phase stability
Unfolded Protein Response in Cancer: IRE1α Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability
The kinase/endonuclease inositol
requiring enzyme 1 (IRE1α),
one of the sensors of unfolded protein accumulation in the endoplasmic
reticulum that triggers the unfolded protein response (UPR), has been
investigated as an anticancer target. We identified potent allosteric
inhibitors of IRE1α endonuclease activity that bound to the
kinase site on the enzyme. Structure–activity relationship
(SAR) studies led to <b>16</b> and <b>18</b>, which were
selective in kinase screens and were potent against recombinant IRE1α
endonuclease as well as cellular IRE1α. The first X-ray crystal
structure of a kinase inhibitor (<b>16</b>) bound to hIRE1α
was obtained. Screening of native tumor cell lines (>300) against
selective IRE1α inhibitors failed to demonstrate any effect
on cellular viability. These results suggest that IRE1α activity
is not essential for viability in most tumor cell lines, in vitro,
and that interfering with the survival functions of the UPR may not
be an effective strategy to block tumorigenesis
Proceedings of the 4th World Conference on Research Integrity
CITATION: O’Brien, S. P., et al. 2016. Proceedings of the 4th World Conference on Research Integrity. Research Integrity and Peer Review, 1:9, doi:10.1186/s41073-016-0012-9.The original publication is available at https://researchintegrityjournal.biomedcentral.comThese Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org).https://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-016-0012-