Endogenous Proteins Modulation in Live Cells with Small Molecules and Light.
Kaixing Zeng1,2, Lili Han1,2, Yiyun Chen1,2,3
1State Key Laboratory of Bioorganic and Natural Products Chemistry, Centre of Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, P. R. China.
Chembiochem : a European Journal of Chemical Biology
|July 13, 2022
Summary
Light-activated small molecules precisely control endogenous proteins in live cells. This chemical biology approach offers new tools for biological research and potential therapeutic applications.
Area of Science:
- Chemical Biology
- Molecular Biology
- Biochemistry
Background:
- Protein function investigation requires precise control over biological processes.
- Genetic methods for protein modulation have limitations in spatiotemporal control.
- Small molecule approaches offer unique advantages for modulating endogenous proteins.
Purpose of the Study:
- To review recent advancements in light-induced endogenous protein modulation using small molecules.
- To highlight the potential of these methods for biological discoveries and therapeutic applications.
- To inspire organic chemists and chemical biologists to explore this field.
Main Methods:
- Infrared-light-induced decaging of small molecules via photolysis.
- Visible-light-induced photocatalytic release of small molecules.
- Small molecule-ligand-directed caging for protein photomodulation.
Main Results:
- Development of three distinct frontiers in small molecule-based protein modulation.
- Enabling high spatiotemporal precision in modulating endogenous proteins.
- Providing powerful chemical biology toolkits for research.
Conclusions:
- Small molecule and light-based methods offer precise spatiotemporal control over endogenous proteins.
- These techniques advance chemical biology and hold therapeutic potential.
- Further exploration is encouraged for new biological discoveries.


