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Tunicamycin is a natural product from Streptomyces bacteria that blocks the first committed step of N-linked glycosylation in eukaryotic cells, which is why labs use it to induce endoplasmic reticulum (ER) stress. It is sold as a mixture of homologues, so no single molecular weight describes “tunicamycin”: the commonly quoted 845.0 applies to tunicamycin VII only. It is a research chemical labelled not for human or veterinary use; this page is general reference, not medical advice or a protocol.
Definition and scope
Tunicamycin is a nucleoside antibiotic isolated from Streptomyces species. A 2025 paper in ACS Central Science describes it as a rare natural-product inhibitor of the PNPT enzyme family. One vendor characterises tunicamycins as active against Gram-positive bacteria, fungi and viruses, but in research labs its main use is as a tool compound for N-glycosylation and the unfolded protein response.
Tunicamycin mechanism of action
In eukaryotes, tunicamycin inhibits DPAGT1 (GlcNAc-1-phosphotransferase), the enzyme that catalyses the first committed step of N-glycosylation: transfer of N-acetylglucosamine phosphate onto dolichol phosphate. The ACS Central Science study reports that the compound’s fatty-acid chain partly mimics the dolichol substrate and that tunicamycin stabilises DPAGT1 against heat far more than the natural substrate does (a melting-temperature shift of 31.3 C versus 5.5 C). Structures of the enzyme with tunicamycin bound are described in the Structural Genomics Consortium DPAGT1 datasheet.
Without the initial dolichol-linked sugar, newly made glycoproteins are not properly glycosylated, which can lead to misfolded protein accumulating in the ER and triggering the unfolded protein response. The same study used nuclear ATF4 as a readout of the ER stress response.
What the ER-stress readout does and does not tell you
- In that study, ER stress (ATF4 induction) had an EC50 of 44 ± 3.2 nM, while cell death had an EC50 of about 10 µM, and ER stress appeared only with the most potent DPAGT1 inhibition. These values are specific to that study’s cell system and compounds and should not be treated as general working concentrations.
- The authors propose, but do not prove, that tuned analogues might separate partial glycosylation blockade from apoptosis.
- Practical consequence: an ER-stress marker, a glycosylation shift and cell death are three different readouts, and a single concentration does not establish which one you are measuring.
Tunicamycin molecular weight
Tunicamycin is not one molecule. Cayman Chemical’s item 11445 is sold as “Tunicamycin Mixture” of congeners, and its listed formula weight of 845.0 (C39H64N4O16) is stated for tunicamycin VII only. The mixture therefore has no single weight that this page can give you.
| Record | What the source states |
|---|---|
| Formula weight, tunicamycin VII | 845.0 (C39H64N4O16), Cayman Chemical item 11445 |
| Product form | Mixture of congeners (Cayman 11445); Sigma-Aldrich T7765 is from Streptomyces sp., purity of at least 98% by HPLC |
| Solubility (Cayman) | DMF 20 mg/ml; DMSO 20 mg/ml; 1:3 DMSO:PBS 0.25 mg/ml |
| Storage | Cayman lists -20 C; Sigma-Aldrich lists 2-8 C |
The two vendors’ storage statements differ, which is the reason to follow the lot-specific certificate of analysis and safety data sheet rather than a general figure. When calculating molarity, record which homologue or mixture and which lot you used.
Lab handling and hazard checklist
- Read the safety data sheet first. The Sigma-Aldrich SDS for T7765 classifies the product as acute toxicity (oral) Category 1, signal word “Danger”, with the skull-and-crossbones pictogram and storage class 6.1A. See how to read a safety data sheet.
- Check your local rules for highly toxic substances. Acute-toxicity chemicals are discussed in particularly hazardous substances in the lab; your Chemical Hygiene Plan determines the local controls.
- Record identity. Note vendor, catalogue number, lot, homologue or mixture, and the storage temperature on that lot’s documents.
- Know the solvent. Vendors list DMSO and DMF as solvents; see the DMSO reference and the lab’s chemical storage segregation rules.
- Keep it to research use. The vendor label states “not for human or veterinary use”.
Common misunderstandings
- “Tunicamycin has a molecular weight of 845.” That figure belongs to one homologue (VII), not the mixture.
- “It is just an antibiotic.” It has antimicrobial activity, but its research role is as a glycosylation inhibitor and ER-stress inducer, and it acts on the eukaryotic enzyme DPAGT1.
- “ER stress means the same thing at every dose.” In the cited study, stress induction and cell death occurred at very different concentrations.
- “Store it like the last bottle.” Vendors state different temperatures; use the document that ships with the lot.
FAQ
What is tunicamycin used for in the lab?
It is used as a tool compound to block N-linked glycosylation and to induce ER stress and the unfolded protein response in cultured cells.
What is the tunicamycin mechanism of action?
It inhibits DPAGT1, which catalyses the first committed step of N-glycosylation, by occupying the substrate sites of the enzyme.
What is the molecular weight of tunicamycin?
It depends on the homologue. Tunicamycin VII has a formula weight of 845.0 (C39H64N4O16) per Cayman Chemical; commercial product is a mixture.
Is tunicamycin hazardous?
The Sigma-Aldrich SDS for T7765 lists acute oral toxicity Category 1 with signal word “Danger”. Follow the SDS for your lot.
Sources
- ACS Central Science 2025, 11, 107-115, lipid-modulated graduated inhibition of N-glycosylation priming: PMC11758266 (read 2026-11-08).
- Structural Genomics Consortium, DPAGT1 target enabling package datasheet (read 2026-11-08).
- Cayman Chemical, Tunicamycin item 11445 (read 2026-11-08).
- Sigma-Aldrich, Safety data sheet T7765 (read 2026-11-08).
