AOD-9604 in Canada: Understanding the hGH 176-191 Fragment
AOD-9604 is one of the more confusingly labelled compounds on the research market. It is sold alongside, and sometimes interchangeably with, “HGH Fragment 176-191”, and the two names do not always describe the same molecule. For labs sourcing AOD-9604 in Canada, especially in multi-vial quantities, it pays to understand exactly which piece of growth hormone the peptide comes from, what was changed, and how to check the vial against the paperwork.
Where the fragment sits in growth hormone
Human growth hormone is a 191-residue protein folded into a four-helix bundle, with two internal disulfide bonds. Its final sixteen residues, positions 176 to 191, form a short C-terminal tail that includes one of those disulfides, linking the cysteines at positions 182 and 189.
In the 1990s, researchers investigating which parts of growth hormone were responsible for its effects on fat metabolism in animal models focused on this C-terminal region. Their working hypothesis was that the tail could be separated from the parts of the protein that bind and activate the growth hormone receptor. Synthetic peptides based on the region followed, and AOD-9604 is the best known of them.
What makes AOD-9604 different from the native tail
The native sequence of hGH 176-191 begins with phenylalanine. AOD-9604 replaces that first residue with tyrosine, giving the 16-residue sequence:
Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe
It can therefore be described either as hGH 177-191 with an added N-terminal tyrosine, or as hGH 176-191 with Phe176 swapped for Tyr. Both descriptions refer to the same peptide. In AOD-9604 the two cysteines are joined by a disulfide bond, as they are in the parent protein, which closes the chain into a loop. Reported figures for this form are a molecular formula of C78H123N23O23S2, a molecular weight of about 1815 g/mol and CAS registry number 221231-10-3.
AOD-9604 vs HGH Fragment 176-191: sorting out the labels
Here is where catalogues get muddled. Products sold as “HGH Fragment 176-191” very often carry the tyrosine-containing sequence as well, not the native phenylalanine version. In that case the only difference from AOD-9604 may be whether the disulfide bond is formed.
| Form | First residue | Cysteines | Approximate mass |
|---|---|---|---|
| Native hGH 176-191 sequence | Phe | Depends on preparation | Lower than the Tyr forms by about 16 Da |
| Tyr-containing fragment, reduced | Tyr | Two free thiols | About 1817 g/mol |
| AOD-9604 (Tyr, disulfide formed) | Tyr | One disulfide bond | About 1815 g/mol |
The 2 Da gap between the reduced and oxidised forms is the mass of the two hydrogen atoms lost when the disulfide forms. It is small, but a decent mass spectrometer resolves it easily, and it is the most direct way to tell the forms apart. The 16 Da difference between tyrosine and phenylalanine comes from tyrosine’s extra hydroxyl oxygen.
For a procurement lead, the lesson is to order by sequence, mass and CAS number, not by trade name. A quote for “Frag 176-191” should state which residue is at the N-terminus and whether the disulfide is formed.
What the published research describes
The literature on AOD-9604 is centred on lipid metabolism in animal models and on adipose tissue and cells in vitro. Papers from the developing group reported effects on lipolysis and lipogenesis in rodent fat tissue, and they reported that the fragment did not act like full-length growth hormone at the growth hormone receptor: it did not compete meaningfully for receptor binding in their assays and did not reproduce the receptor-driven signalling associated with the whole hormone. Some rodent studies proposed involvement of beta-3 adrenergic receptor pathways, although the mechanism was not fully settled.
As with any narrowly studied compound, most of this work comes from a small number of groups, and researchers designing new experiments should treat the proposed mechanisms as working hypotheses.
Checking AOD-9604 shipments in Canada on arrival
When a multi-vial order arrives, a short receiving routine catches the naming problems described above:
- Confirm that the label says AOD-9604, or that a fragment label specifies the Tyr sequence and disulfide status.
- Compare the mass on the certificate, where one is published, with roughly 1815 g/mol for the disulfide form.
- Match the vial’s cap and crimp colour to the certificate and record the pairing.
- Count vials against the packing slip, note the appearance of the freeze-dried solid, and store cold and dark the same day.
Handling notes for the analytical lab
Disulfide-containing peptides bring a couple of specific precautions to analytical work:
- Avoid reducing agents such as DTT or TCEP in sample preparation unless you intend to break the disulfide, since they convert the peptide to the reduced form and shift its mass and retention.
- Watch for dimers. Free thiols in a partly reduced sample can pair up between molecules, producing species at roughly double the mass.
- Expect two peaks if the sample is mixed. The oxidised and reduced forms usually separate on reversed-phase HPLC, so an unexpected shoulder may simply be the other form.
Keeping analytical solutions slightly acidic and using them promptly limits disulfide exchange during a run.
Volume ordering and testing
Bulk Peptides stocks AOD-9604 in 5 mg vials. If a study will use it over several months, request enough vials from one lot to cover the work and log each vial group against its certificate reference. Our products are third-party tested for purity by HPLC, certificates are published for some products, and vials are matched to their certificate by cap and crimp colour. Vial pricing is mix-and-match, so every vial in the cart counts toward the volume break, and orders ship from within Canada.
AOD-9604 is sold by Bulk Peptides for in-vitro laboratory research only. It is not for human or animal use, and nothing in this article should be read as guidance on use in people or animals.
