Program in Chemical Biology, Sloan Kettering Institute, New York, NY 10065, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
STAR Protoc. 2022 Apr 19;3(2):101318. doi: 10.1016/j.xpro.2022.101318. eCollection 2022 Jun 17.
Epichaperomes are disease-associated pathologic scaffolds composed of tightly bound chaperones and co-chaperones. They provide opportunities for precision medicine where aberrant protein-protein interaction networks, rather than a single protein, are detected and targeted. This protocol describes the synthesis and characterization of two I-labeled epichaperome probes, [I]-PU-H71 and [I]-PU-AD, both which have translated to clinical studies. It shows specific steps in the use of these reagents to image and quantify epichaperome-positivity in tumor bearing mice through positron emission tomography. For complete details on the use and execution of this protocol, please refer to Bolaender et al. (2021), Inda et al. (2020), and Pillarsetty et al. (2019).
Epichaperomes 是由紧密结合的伴侣蛋白和共伴侣蛋白组成的与疾病相关的病理支架。它们为精准医学提供了机会,在这种医学中,检测和靶向的是异常的蛋白质-蛋白质相互作用网络,而不是单个蛋白质。本方案描述了两种 I 标记的 Epichaperome 探针[I]-PU-H71 和[I]-PU-AD 的合成和表征,这两种探针都已转化为临床研究。它展示了使用这些试剂通过正电子发射断层扫描对荷瘤小鼠进行 Epichaperome 阳性成像和定量的具体步骤。有关该方案使用和执行的完整详细信息,请参见 Bolaender 等人(2021 年)、Inda 等人(2020 年)和 Pillarsetty 等人(2019 年)。