Flagothier Jessica, Kaisin Geoffroy, Mercier Frederic, Thonon David, Teller Nathalie, Wouters Johan, Luxen André
Department of Chemistry, University of Liege (ULg), 13 allée du 6 aout, B-4000 Liege (Sart-tilman), Belgium.
Appl Radiat Isot. 2012 Aug;70(8):1549-57. doi: 10.1016/j.apradiso.2012.04.022. Epub 2012 Apr 27.
Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [(18)F] labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two new linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [(18)F] prosthetic group.
寡核苷酸（ONs），尤其是小干扰RNA（siRNAs）是很有前景的药物，但它们的药代动力学和生物分布却鲜为人知。使用氟 - 18的正电子发射断层扫描（PET）是一种用于量化这些生物学过程的合适技术。点击化学（惠斯根环加成反应）是目前标记小干扰RNA的方法。为了研究[(18)F]标记的寡核苷酸所携带的连接子对体内药代动力学和代谢的影响，我们通过两种新的连接子开发了两种修饰的寡核苷酸。在此，我们报告了两种含炔基连接子的合成、将其掺入寡核苷酸以及通过点击化学与[(18)F]辅基进行共轭的过程。
