Chemical proteomics suggests sofosbuvir is metabolically attached to proteins through a UMPylation-like pathway.

Hertwig, M.; Kielkowski, P.

doi:10.64898/2026.10.17.759838

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bioRxiv · 10.64898/2026.10.17.759838

Chemical proteomics suggests sofosbuvir is metabolically attached to proteins through a UMPylation-like pathway.

Hertwig, M.·Kielkowski, P.

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Abstract

Sofosbuvir is a pronucleotide prodrug (ProTide) that releases a uridine monophosphate analogue, which could modify proteins chemically or through UMP-transferring enzymes. Using an alkyne-tagged probe and chemical proteomics, we identified about 120 labelled proteins and a UMPylation-like (+774.31 Da) modification on cathepsin Z, suggesting that nucleotide prodrugs may enter protein nucleotidylation pathways.

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Hertwig, M., Kielkowski, P.. 2026-10-20. Chemical proteomics suggests sofosbuvir is metabolically attached to proteins through a UMPylation-like pathway.. https://doi.org/10.64898/2026.10.17.759838

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