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PreprintCC BYChemRxiv

Steroid Thioesters to Target Golgi Apparatus

Abstract

Despite Golgi apparatus plays a central role in lipid and protein trafficking, the biomedical potential of Golgitargeting supramolecular assemblies remains underexplored. While recent studies showed that peptide thioesters localize to the Golgi, it is unclear whether steroid thioesters can exhibit similar targeting behavior. Here, we designed and synthesized steroid-based thioesters by conjugating a thioester group and an NBD fluorophore to bile acids (BAs). Live-cell fluorescence imaging revealed that steroid thioesters localize to the Golgi apparatus, further confirming the utility of thioesters as a reactive warhead for Golgi targeting via localized S-palmitoylation. While BA-thioesters accumulate at the Golgi, their accumulation is slower than peptide thioesters. Unlike the peptide thioesters, these steroid conjugates displayed excellent cellular compatibility, showing minimal cytotoxicity. O-acetylation of BAs also modulates the dynamics of Golgi targeting. Our findings demonstrate that steroid thioesters can serve as Golgi-targeting motifs, expanding the pool of organelle-directed bioconjugates and providing a new scaffold for the design of functional molecules to reprogram palmitoylation-associated processes.

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BibTeX
@misc{zou2026steroid,
  title = {{Steroid Thioesters to Target Golgi Apparatus}},
  author = {Linrui Zou and Weiyi Tan and Qiuxin Zhang and Bing Xu},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010486/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010486/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Steroid Thioesters to Target Golgi Apparatus
AU  - Linrui Zou
AU  - Weiyi Tan
AU  - Qiuxin Zhang
AU  - Bing Xu
PY  - 2026
DA  - 2026/10/14
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010486/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010486/v1
AB  - Despite Golgi apparatus plays a central role in lipid and protein trafficking, the biomedical potential of Golgitargeting supramolecular assemblies remains underexplored. While recent studies showed that peptide thioesters localize to the Golgi, it is unclear whether steroid thioesters can exhibit similar targeting behavior. Here, we designed and synthesized steroid-based thioesters by conjugating a thioester group and an NBD fluorophore to bile acids (BAs). Live-cell fluorescence imaging revealed that steroid thioesters localize to the Golgi apparatus, further confirming the utility of thioesters as a reactive warhead for Golgi targeting via localized S-palmitoylation. While BA-thioesters accumulate at the Golgi, their accumulation is slower than peptide thioesters. Unlike the peptide thioesters, these steroid conjugates displayed excellent cellular compatibility, showing minimal cytotoxicity. O-acetylation of BAs also modulates the dynamics of Golgi targeting. Our findings demonstrate that steroid thioesters can serve as Golgi-targeting motifs, expanding the pool of organelle-directed bioconjugates and providing a new scaffold for the design of functional molecules to reprogram palmitoylation-associated processes.
ER  -