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Issue 4, 2020
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Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint

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Abstract

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.

Graphical abstract: Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint

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Supplementary files

Article information


Submitted
15 May 2020
Accepted
04 Aug 2020
First published
27 Aug 2020

This article is Open Access

RSC Chem. Biol., 2020,1, 214-224
Article type
Paper

Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint

K. Hu, L. Xie, M. Hanyu, Y. Zhang, L. Li, X. Ma, K. Nagatsu, H. Suzuki, W. Wang and M. Zhang, RSC Chem. Biol., 2020, 1, 214
DOI: 10.1039/D0CB00070A

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