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Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint
RSC Chemical Biology Pub Date : 2020-08-27 , DOI: 10.1039/d0cb00070a
Kuan Hu 1 , Lin Xie 1 , Masayuki Hanyu 1 , Yiding Zhang 1 , Lingyun Li 2 , Xiaohui Ma 3 , Kotaro Nagatsu 1 , Hisashi Suzuki 1 , Weizhi Wang 2 , Ming-Rong Zhang 1
Affiliation  

Interface peptides that mediate protein–protein interactions (PPI) are a class of important lead compounds for designing PPI inhibitors. However, their potential as precursors for radiotracers has never been exploited. Here we report that the interface peptides from programmed death-ligand 1 (PD-L1) can be used in positron emission tomography (PET) imaging of programmed cell death 1 (PD-1) with high accuracy and sensitivity. Moreover, the performance differentiation between murine PD-L1 derived interface peptide (mPep-1) and human PD-L1 derived interface peptide (hPep-1) as PET tracers for PD-1 unveiled an unprecedented role of a non-critical residue in target binding, highlighting the significance of PET imaging as a companion diagnostic in drug development. Collectively, this study not only provided a first-of-its-kind peptide-based PET tracer for PD-1 but also conveyed a unique paradigm for developing imaging agents for highly challenging protein targets, which could be used to identify other protein biomarkers involved in the PPI networks.

中文翻译:

利用 PD-L1 界面肽对 PD-1 免疫检查点进行正电子发射断层扫描成像

介导蛋白质-蛋白质相互作用 (PPI) 的界面肽是一类用于设计 PPI 抑制剂的重要先导化合物。然而,它们作为放射性示踪剂前体的潜力从未被开发出来。在这里,我们报告了程序性死亡配体 1 (PD-L1) 的界面肽可用于程序性细胞死亡 1 (PD-1) 的正电子发射断层扫描 (PET) 成像,具有高精度和灵敏度。此外,鼠 PD-L1 衍生界面肽 (mPep-1) 和人 PD-L1 衍生界面肽 (hPep-1) 作为 PD-1 的 PET 示踪剂之间的性能差异揭示了非关键残基在靶​​标中的前所未有的作用结合,突出了 PET 成像作为药物开发中伴随诊断的重要性。总的来说,
更新日期:2020-10-08
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