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Small-Molecule Benzo-Phenoselenazine Derivatives for Multi-Subcellular Biomolecule Profiling.

Han Jia1, Jinghua Han1, Yajing Qi2

  • 1Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China.

Angewandte Chemie (International Ed. in English)
|November 29, 2024
PubMed
Summary

Researchers developed a new small-molecule method using selenium-containing Nile Blue (SeNB) derivatives for proximity labeling. This technique maps RNA and protein locations in living cells without genetic modification, revealing organelle membrane preferences.

Keywords:
lipid membranesnear-infrared (NIR) lightproteomicsproximity labelingtranscriptomics

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Understanding subcellular localization of RNAs and proteins is crucial for biological function.
  • Genetically encoded probes are limited to specific cell lines.
  • Existing small-molecule methods lack comprehensive profiling capabilities for multiple locations in living cells.

Purpose of the Study:

  • To introduce a novel, genetics-free proximity labeling strategy for profiling RNA and protein localization in living cells.
  • To investigate the capabilities of benzo-phenoselenazine derivatives for selective subcellular labeling.
  • To explore the potential of this method for elucidating inter-organelle interactions and its implications for disease research.

Main Methods:

  • Development of selenium-containing Nile Blue (SeNB) derivatives for proximity labeling.
  • Near-infrared light activation in the presence of propargylamine to generate singlet oxygen.
  • In vitro, computational, and in cellulo examinations of SeNB compound performance.
  • Proteomic and transcriptomic analyses to study inter-organelle interactions.

Main Results:

  • SeNB derivatives enable selective labeling of RNAs and proteins within living cells.
  • The compounds show a distinct preference for labeling organelle membranes.
  • The method provides deep penetration and high spatial resolution for subcellular localization.
  • SeNB derivatives successfully elucidated inter-organelle interactions at the molecular level.

Conclusions:

  • SeNB derivatives offer a wash-free and genetics-free approach for illuminating subcellular localization.
  • This novel strategy provides deep penetration and high spatial resolution, surpassing current limitations.
  • The findings hold significant potential for advancing cellular process understanding in disease and therapeutics.