Chemical tools targeting purine-binding membrane proteins involved in inflammation, immunity, and ca
Vortragende: Prof. Christa E. Müller
Ort: L.EG.200, Universität Innsbruck, CCB, Innrain 80-82
Extracellular adenosine triphosphate (ATP) acts as a pro-inflammatory danger signal via activation of purine P2Y and P2X receptors. In contrast, its corresponding nucleoside adenosine is a strongly immunosuppressive agent activating G protein-coupled P1 (adenosine) receptors.
Cancer tissues can release large amounts of the nucleotide ATP, which is immediately hydrolyzed by ectonucleotidases, upregulated on many cancer cells, leading to the production of adenosine. Activation of adenosine A2A and A2B receptors results in antiproliferative, angiogenic, pro-metastatic, and strongly immunosuppressive effects. The balance between the impact of pro-inflammatory ATP and anti-inflammatory adenosine can be modulated by ectonucleotidase inhibitors, or by activation or blockade of purine receptor subtypes. Recent progress of our laboratory in the identification and optimization of purine receptor antagonists and ectonucleotidase inhibitors by convergent approaches, utilizing structural biology, will be presented.
These tool compounds, including labeled derivatives, are used to study their targets’ role in health and disease. Moreover, they have potential for further development as novel drugs.