Schilson Stefanie S, Keul Petra, Shaikh Rizwan S, Schäfers Michael, Levkau Bodo, Haufe Günter
Organic Chemistry Institute, University of Münster, Corrensstraße 40, D-48149 Münster, Germany.
Institute for Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital, Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
Bioorg Med Chem. 2015 Mar 1;23(5):1011-26. doi: 10.1016/j.bmc.2015.01.014. Epub 2015 Jan 16.
Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [(18)F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases.
鞘氨醇-1-磷酸（S1P）通过与五个G蛋白偶联受体家族（S1P1 - 5）相互作用，影响各种基本生物学过程。FTY720是一种鞘氨醇类似物，已被批准用于治疗复发型多发性硬化症，它在体内被磷酸化，并作为五种S1P受体亚型中四种的激动剂。从这些先导结构出发，我们开发了S1P1受体的新型激动剂。在体内测试了其生物活性，并对有前景的配体在不同位置进行氟化，以确定[(18)F]标记后用于正电子发射断层扫描（PET）成像的候选物。这些放射性配体应能够在体内对S1P1受体表达进行成像，因此可作为S1P相关疾病的新型成像标志物。
