Ruthenium Half‐Sandwich Complexes Bound to Protein Kinase Pim‐1J.E. Debreczeni, Alex N. Bullock, G. Ekin Atilla et al.|Angewandte Chemie International Edition|2006 Keeping in shape with half a sandwich: The structure of a picomolar organoruthenium inhibitor bound to the ATP-binding site of the protein kinase Pim-1 (see picture) demonstrates that the ruthenium center has solely a structural role in organizing the organic ligands in the three-dimensional receptor space, thus yielding a structure that is complementary in shape and functional group presentation to the active site of Pim-1.
An Organometallic Inhibitor for Glycogen Synthase Kinase 3Howard Bregman, Douglas S. Williams, G. Ekin Atilla et al.|Journal of the American Chemical Society|2004 Replacing natural products with kinetically inert metal complexes may lead to a new class of therapeutics in which a metal center plays the role of an innocent bystander, organizing the orientation of the organic ligands in the receptor space. As an example of this approach, a ruthenium complex is described that copies the binding mode of indolocarbazole protein kinase inhibitors and serves as a reversible, low-nanomolar inhibitor for glycogen synthase kinase 3 (GSK-3).
Switching on a Signaling Pathway with an Organoruthenium ComplexDouglas S. Williams, G. Ekin Atilla, Howard Bregman et al.|Angewandte Chemie International Edition|2005 Like an organic molecule! A chemically inert ruthenium complex acts as a metallopharmaceutic inhibitor of the protein kinase GSK-3 by targeting its ATP-binding site. It is shown to switch on the Wnt signal transduction pathway inside living cells and in Xenopus embryos, which developed a hyperdorsalized phenotype (see picture, top; bottom: control specimen) on administration of the complex. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462501_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Ruthenium Half‐Sandwich Complexes Bound to Protein Kinase Pim‐1Ein halber Sandwich hält in Form: Die Struktur eines pikomolaren Organorutheniuminhibitors an der ATP-Bindungsstelle der Proteinkinase Pim-1 zeigt, dass dem Rutheniumzentrum nur eine strukturgebende Rolle zufällt: Es richtet die organischen Liganden so aus, dass Form und Anordnung der funktionellen Gruppen komplementär zum aktiven Zentrum von Pim-1 sind (siehe Bild).
Switching on a Signaling Pathway with an Organoruthenium ComplexWie ein organisches Molekül! Ein chemisch inerter Rutheniumkomplex, der die Proteinkinase GSK-3 an ihrer ATP-Bindungsstelle inhibiert, schaltet den Wnt-Signalweg in lebenden Zellen und in Xenopus-Embryos ein. Diese entwickeln bei Verabreichung des neuen Metallopharmazeutikums einen hyperdorsalisierten Phänotyp (im Bild oben; unten: Kontrollexemplar). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z462501_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.