Description
PrymaLab · Research Use Only
ARA-290 10mg
Designed against a receptor that has no gene of its own
Most compounds in this catalogue engage a receptor that can be named, cloned and knocked out. ARA 290 peptide was designed against something less settled than that. Its proposed target is a partnership between two chains rather than a protein in its own right, and the case for it rests on function rather than on structure.
Specification Table
| Property | Value |
|---|---|
| Compound | ARA-290 |
| International non-proprietary name | Cibinetide |
| CAS number | Not stated here. No registration was traced to a primary source during preparation |
| Residue count | Eleven |
| Sequence | pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser |
| N terminus | Pyroglutamate, a cyclised glutamine or glutamate |
| Molecular weight | Approximately 1257 g/mol. Confirm against the lot certificate |
| Parent molecule | Human erythropoietin, a 165-residue glycoprotein |
| Derivation | The helix B surface domain of the parent |
| Relationship to the parent | A surface mimetic. It reproduces a three-dimensional face rather than a linear motif |
| Proposed target | A complex of the erythropoietin receptor with the beta common receptor, CD131 |
| Genetic status of that target | No separate gene. It is a proposed association of two independently encoded chains |
| Competing mechanism | A separate published report describes activity at a TRPV1 channel |
| Regulatory status | Not approved. Orphan designation has been granted for one indication |
| Vial | 10mg lyophilized |
| Storage | Sealed at minus 20°C. Protect from moisture |
What Is the ARA 290 Peptide Target?
ARA 290 peptide was designed to engage what its originators named the innate repair receptor.
The proposal is that erythropoietin signals through two distinct receptor arrangements. One is the familiar homodimer of the erythropoietin receptor, which drives red cell production. The other is a complex of that receptor with a second chain, the beta common receptor, also written CD131.
Brines and colleagues set out the evidence for that second arrangement and designed peptides intended to engage it without engaging the first.
This compound is one of those peptides, and the design objective was to keep the protective signalling and lose the erythropoietic activity.
It is worth being precise about what kind of entity that target is.
It is not a protein with its own gene. There is a gene for the erythropoietin receptor and a gene for the beta common receptor, and the proposed target is an association between their products.
That is not unusual in itself. Plenty of receptors work as heteromers, and several are well characterised.
What is unusual here is how much of the case rests on functional evidence rather than on structural evidence, which is the subject of the next section.
Why Does That Distinction Matter?
The receptor ARA 290 peptide targets is not that kind of entity. A receptor with its own gene can be deleted cleanly, expressed alone in a null background, and its structure solved.
A proposed heteromer offers none of those things straightforwardly.
Deleting either chain removes the complex and also removes everything else that chain does, so a knockout result is harder to attribute than it looks.
Expressing the complex requires both chains and a demonstration that they associate in the system used, which is an extra assumption in every experiment.
Structural work on a transient association between two membrane proteins is considerably harder than on a single receptor, and the absence of a resolved structure is not evidence against the proposal.
It does mean the target is described rather than defined.
For a researcher the practical consequence is that a positive result cannot be reported as engagement of a receptor in the way it could for a conventional target.
It can be reported as an effect consistent with the proposed mechanism, which is a weaker claim and the one the evidence supports.
Designing around this means running the compound in systems where each chain can be manipulated separately, and accepting that the interpretation will be an argument rather than a readout.
Is There More Than One Mechanism on Offer?
Yes, and this is the part most listings for this compound leave out.
A separate published line of work reports that the compound acts at TRPV1, an ion channel with no relationship to the erythropoietin receptor family.
That is not a refinement of the original proposal. It is a different mechanism at a different class of target.
Two possibilities follow and the published record does not decide between them.
The compound may engage both, which would make it a less selective tool than the design intent suggests and would mean effects attributed to one target may belong to the other.
Or one of the two reports may not generalise beyond the systems it was demonstrated in, which happens regularly and is not a criticism of either group.
What a researcher can do with this is straightforward. Any design should include a control that distinguishes the two, and the simplest is a TRPV1 antagonist run alongside.
Reporting an effect without that control leaves a reader unable to tell which mechanism the result speaks to, and on this compound that is not a hypothetical objection.
A word on how to hold two competing mechanism claims without dismissing either.
Neither report is fringe work and neither has been retracted.
The situation is ordinary for a compound that has not been through a full development programme, where the target is usually settled by the sheer volume of work rather than by any single experiment.
What is unusual is how rarely the second claim is mentioned in commercial descriptions of this compound, which present the original proposal as though it were the only one.
What Does Surface Mimicry Mean Structurally?
The relationship between ARA 290 peptide and its 165 residue parent is not the usual fragment relationship.
A conventional fragment reproduces a stretch of sequence that carries the interaction. This one reproduces a face.
Helix B of erythropoietin presents an outward-facing surface, and the residues that form that surface are not contiguous in the folded protein in the way a linear reading suggests.
A peptide built from that region therefore mimics a spatial arrangement rather than copying a functional motif, which is a harder thing to do and a more fragile one.
The fragility is the point worth carrying into an experiment.
A short linear peptide in solution samples a wide range of conformations, and only some of them resemble the surface it was designed from.
That means the effective concentration of the active conformation is lower than the nominal concentration of the peptide, by an amount nobody can measure directly.
It also means anything that shifts the conformational distribution, including temperature, ionic strength and the presence of organic solvent, can change the apparent potency without changing how much peptide is present.
The nasal spray page in this catalogue covers the chemical stability side of this molecule in more depth than a vial page should. What is worth adding here is that conformational behaviour is a second variable alongside chemical integrity, and a certificate speaks only to the first.
One consequence of that conformational argument is worth drawing out because it affects reproducibility directly.
Two laboratories using identical nominal concentrations in different buffers are not running the same experiment.
On a folded protein that statement would be an overreach. On a short peptide whose activity depends on transiently adopting a particular shape, it is a description of the situation.
Recording the buffer fully, rather than as a name, is what makes a result comparable.
What Should the Certificate Show?
The full eleven residue sequence written out, including the pyroglutamate at the N terminus.
Confirmation that the terminus is cyclised rather than open, since the open form is a different molecule with a different mass.
Observed mass by spectrometry against the calculated figure, with the salt form stated separately.
Purity by chromatography with the method named.
Net peptide content, because the vial mass includes counterion and residual water.
The deamidation state, which matters on a sequence carrying an asparagine next to a serine.
Lot number and manufacturing date.
The pyroglutamate line is the one worth insisting on. It forms readily and it can also be absent, and a preparation with an open N terminus is a distinct species that a purity percentage alone will not reveal.
It is also worth asking for the counterion by name rather than accepting the word salt, since trifluoroacetate carries documented effects of its own in cell systems and acetate does not.
That question costs nothing to ask and the answer occasionally changes which lot a laboratory buys.
How Should the Vial Be Handled?
ARA 290 peptide has no cysteine, no methionine and no tryptophan, which makes it chemically undemanding by the standards of this catalogue.
Sealed lyophilized powder holds at minus 20 degrees Celsius, protected from moisture.
Bring the vial to ambient temperature before opening, since the powder takes up water readily and cold glass condenses room air onto it.
Reconstitute gently by adding diluent down the wall and allowing it to stand.
Keep prepared solutions near neutral pH and cold. The asparagine and serine pair is the hydrolytic liability and both extremes of pH accelerate it.
Aliquot on first reconstitution rather than freezing and thawing a working stock.
Use low-binding consumables. The sequence carries several glutamates and one arginine, so it is charged at working pH and will adsorb at dilute concentrations.
Keep the vehicle constant across an experiment. Because the active conformation is a small fraction of what is present, a change of buffer is a change of effective concentration even at identical nominal concentration.
Record lot, net peptide content, diluent, buffer and ionic strength, storage temperature and date.
Ionic strength belongs in that list on this compound specifically, and it is the field almost nobody records.
None of this is onerous. It is a short list, and the only item on it that differs from ordinary practice is the one about holding the vehicle constant.
Published Literature
Selected references on the tissue-protective peptide programme, on the proposed receptor arrangement, on the competing mechanism report and on peptide storage generally.
- Brines M, Patel NS, Villa P, Brines C, Mennini T, De Paola M, et al. Proceedings of the National Academy of Sciences. 2008;105(31):10925-10930. DOI: 10.1073/pnas.0805594105
- Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, et al. Proceedings of the National Academy of Sciences. 2004;101(41):14907-14912. DOI: 10.1073/pnas.0406491101
- Brines M, Cerami A. Journal of Internal Medicine. 2008;264(5):405-432. DOI: 10.1111/j.1365-2796.2008.02024.x
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Pharmaceutical Research. 2010;27(4):544-575. DOI: 10.1007/s11095-009-0045-6
Frequently Asked Questions
What is ARA-290?
ARA 290 peptide is an eleven residue synthetic sequence derived from the helix B surface domain of erythropoietin, also known as cibinetide, with a pyroglutamate N terminus and a mass near 1257.
What is it designed to engage?
A complex described as the innate repair receptor, proposed to consist of the erythropoietin receptor associated with the beta common receptor, CD131.
Does that complex have its own gene?
No. There is a gene for each chain and the proposed target is an association between their products, which is why it is described rather than defined.
Why does that complicate an experiment?
Deleting either chain removes the complex and everything else that chain does. Expressing it requires both chains plus a demonstration that they associate in the system used.
Can a result be reported as receptor engagement?
Not in the way it could for a conventional target. It can be reported as an effect consistent with the proposed mechanism, which is what the evidence supports.
Is there a competing mechanism?
Yes. A separate published line of work reports activity at TRPV1, an ion channel unrelated to the erythropoietin receptor family. That is a different mechanism, not a refinement.
How should a design handle that?
By including a control that distinguishes the two. A TRPV1 antagonist run alongside is the simplest, and without it a reader cannot tell which mechanism a result speaks to.
What does surface mimicry mean?
The peptide reproduces a three-dimensional face of the parent rather than copying a contiguous functional motif. That is harder to achieve and more fragile in solution.
Why does fragility matter practically?
A short linear peptide samples many conformations and only some resemble the designed surface, so the effective concentration of the active form is lower than the nominal concentration.
What changes the apparent potency?
Anything that shifts the conformational distribution, including temperature, ionic strength and organic solvent, can move apparent potency without changing how much peptide is present.
What must the certificate confirm?
The full sequence, that the N terminus is cyclised to pyroglutamate rather than open, observed mass, purity with the method named, net peptide content and the deamidation state.
What belongs in the record?
Lot, net peptide content, diluent, buffer, ionic strength, storage temperature and date. Ionic strength matters here because the active conformation is a small fraction of what is present.
Compliance Statement
ARA-290 is sold exclusively for laboratory research use. It is not a drug, food, or cosmetic product, and it is not a dietary product of any kind. It is not approved by the FDA or any comparable authority for human or veterinary use, it is not approved by any authority and holds only an orphan designation for a single indication, its proposed target is an association between two independently encoded chains rather than a separately encoded receptor and is therefore described rather than defined, a competing mechanism at an unrelated target has been published alongside the original proposal and the record does not decide between them, and no compound in this range is offered for any human or veterinary purpose. This product is not intended to diagnose, treat, cure, or prevent any disease. It must not be given to humans or animals. Purchase is restricted to qualified researchers and institutions operating within applicable laws. All handling is the responsibility of the purchasing laboratory.
Other formats of ARA-290
ARA-290 is also stocked as ARA-290 10mg Nasal Spray and ARA-290 (Cibinetide) 10mg preloaded 3ml pen. Each listing states its own quantity and concentration, and the pen and vial comparison explains what changes between formats. The ARA-290 sourcing guide covers what to check on a certificate before ordering.
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