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Related Experiment Video

Updated: Apr 5, 2026

Author Spotlight: Combining Proximity Ligand Assay with Gamma-H2AX Staining to Characterize Protein Interactions in DNA Damage Response

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Photocatalytic proximity labeling in primary samples.

Haotian Guo¹, Xinyuan Fan¹

¹Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Current Opinion in Chemical Biology

|April 3, 2026

Summary

Photocatalytic proximity labeling (PPL) offers a non-genetic method to study molecular interactions in primary samples. This technique uses light-activated catalysts for precise biomolecule tagging, advancing in situ biological research.

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Area of Science:

Biochemistry
Molecular Biology
Cell Biology

Background:

Primary samples are crucial for understanding health and disease due to their native states.
Conventional proximity labeling (PL) methods are limited in primary samples due to genetic manipulation requirements.
Photocatalytic proximity labeling (PPL) offers a non-genetic, light-activated alternative for in situ molecular analysis.

Purpose of the Study:

To review recent advancements in applying PPL to primary biological samples.
To highlight PPL's potential in various applications, including organelle proteomics and cell-cell interactions.
To discuss challenges and opportunities for PPL in native biological contexts.

Main Methods:

Summarizing recent developments in photocatalytic systems and probe chemistries for PPL.
Reviewing PPL applications in organelle-resolved proteomics, cell surface profiling, and tissue analysis.
Discussing strategies for catalyst targeting and long-wavelength activation.

Main Results:

PPL enables temporally gated and spatially localized covalent tagging of biomolecules in primary samples.
Applications span organelle proteomics, cell surface interactions, tissue analysis, and immune engineering.
Growing diversity of photocatalytic systems and probes, though deployment in primary samples is nascent.

Conclusions:

PPL shows significant promise for interrogating native biological systems without genetic modification.
Advances in reaction chemistry and catalyst targeting are addressing challenges in primary sample applications.
Further development of PPL toolkits for primary samples will enhance insights into cellular organization and disease mechanisms.