Molecule guides
What Is CJC-1295 with DAC? Albumin Conjugation, GHRH Receptor Pharmacology and Research Use
The long-acting GHRH analogue explained: how its maleimide linker latches onto albumin Cys34, what days-long receptor occupancy changes, and how to handle and verify the material.
CJC-1295 with DAC takes the Modified GRF 1-29 sequence and adds a lysine at position 30 bearing a maleimidopropionyl group — the drug affinity complex (DAC). This group forms a covalent bond with the free thiol on cysteine-34 of circulating serum albumin, turning a peptide that would be cleared within minutes into one that remains for days. The chemistry defines the compound. Every feature that separates CJC-1295 with DAC from its non-DAC counterpart stems from that single maleimide, as does its role in research: it is the tool of choice when an experiment needs sustained GHRH receptor occupancy instead of a brief pulse.
Below we cover the conjugation chemistry, the receptor mechanism, the consequences of continuous exposure, and how the material is specified and handled.
Design and structure: how the DAC linker works
Serum albumin is plasma's most plentiful protein, it survives in the circulation for about three weeks, and it has exactly one free cysteine thiol, at position 34 — the only unpaired cysteine in the protein. Together these features make it an exceptionally handy anchor for prolonging the lifetime of a small peptide, which is precisely what the DAC strategy exploits.
Maleimides combine with thiols through Michael addition to give a stable thioether linkage, and at near-neutral pH they do so highly selectively. A peptide carrying a maleimidopropionyl group will therefore seek out and bind albumin's Cys34 once it enters the circulation. The resulting conjugate is much too large to be filtered by the kidneys and is protected from most peptidases, so its clearance tracks albumin turnover rather than that of the peptide.
The details of the design are important. The maleimide sits on an extra lysine at position 30, beyond the C-terminal end of the 1–29 receptor-binding sequence, keeping the reactive group as far as possible from the residues that contact the receptor. The underlying backbone is Modified GRF 1-29 — D-alanine at 2, glutamine at 8, alanine at 15 and leucine at 27 — so the DAC form keeps all the chemical stability of that substituted analogue and gains albumin binding in addition. The molecular weights make this plain: 3647.28 g/mol versus 3367.93 g/mol without DAC, a gap of about 279 Da accounted for by the extra lysine and linker.
Mechanism of action
At the receptor, nothing differs from other GHRH analogues: binding to the GHRH receptor on pituitary somatotrophs activates Gs, increases cAMP and switches on protein kinase A, boosting transcription and secretion of growth hormone.
What differs is the exposure profile. Native GHRH and sermorelin give a spike lasting minutes; Modified GRF 1-29 gives a somewhat longer pulse; the albumin-bound form gives a plateau lasting days, with multi-day half-lives reported in animal studies and in early human pharmacokinetic work from its development. That makes it a fundamentally different pharmacological experiment, and the literature is clear about the implications: prolonged agonist occupancy at a class B GPCR tends to cause receptor desensitisation and downregulation, and it abolishes the pulsatility typical of normal somatotropic axis function.
For researchers, that is exactly the value. If the question is how continuous GHRH receptor activation affects somatotroph signalling, receptor expression or downstream IGF-1, a long-acting agonist is the right instrument and a short-acting one is not; for questions about pulsatile physiology, the opposite applies. Choosing between the two forms is a matter of study design, not taste, and the trade-offs are discussed in CJC-1295 vs CJC-1295 with DAC.
Research applications
Pharmacokinetics and sustained receptor occupancy
The original development programme produced animal and early-phase human pharmacokinetic data confirming the multi-day persistence the DAC conjugation was built to achieve, along with prolonged increases in growth hormone and IGF-1 markers. The programme was not taken through to approval, and no CJC-1295 product has marketing authorisation in any jurisdiction.
Receptor desensitisation and axis regulation
How continuous and pulsatile agonist exposure differ is a general question in class B GPCR pharmacology, and long-acting GHRH analogues are an obvious tool for addressing it. Typical endpoints are receptor expression, cAMP responsiveness on re-challenge and the behaviour of downstream IGF-1.
Comparative structure–activity studies
The DAC and non-DAC forms differ by one structural feature only, making them an ideal pair for separating the effect of exposure duration from that of receptor pharmacology — an unusually well-controlled comparison for peptide research.
Combination designs
Combining a GHRH receptor agonist with a ghrelin-receptor (GHS-R1a) agonist such as ipamorelin is a frequent design, because both receptors are on the same cell and signal through different second messengers. Pre-blended research material is available as CJC-1295 DAC with ipamorelin. Pairing a long-acting and a short-acting agonist creates a more complex exposure profile than either compound alone, and methods sections should say so explicitly.
Available formats and vial sizes
We supply CJC-1295 with DAC as lyophilized powder in sealed vials of 2 mg (€55), 5 mg (€100) and 10 mg (€180). At 3647.28 g/mol, 5 mg corresponds to about 1.37 micromoles — a little less than the 1.48 micromoles in 5 mg of the non-DAC form, which should be factored into any molar-matched comparison. The family is listed under GHRH analogs.
Reconstitution and storage at the bench
Worked example: dissolving a 5 mg vial in 2 mL of bacteriostatic water gives 2.5 mg/mL (2,500 mcg/mL), and 0.1 mL — 10 units on a U-100 syringe scale — contains 250 mcg. In molar terms, the stock is roughly 686 micromolar.
One handling issue is unique to this molecule and outweighs the rest: the maleimide is reactive toward any accessible thiol, not just albumin. Buffers and diluents with reducing agents such as dithiothreitol or beta-mercaptoethanol will use it up, as will free cysteine or thiol-bearing supplements in culture media. Maleimides also hydrolyse gradually in water — faster at alkaline pH — steadily eroding their ability to conjugate. In practice, reconstitute in a thiol-free diluent at near-neutral pH, avoid keeping the peptide in solution for long, and store aliquots frozen. Keep lyophilized vials at −20 °C or below, away from light and moisture. Our peptide storage guide gives general advice.
Purity and reading the certificate of analysis
Every lot is purified by reversed-phase HPLC to 99% or higher, confirmed by mass and supplied with a certificate matched to the lot. Mass is the decisive test. The measured value should agree with 3647.28 g/mol; a result close to 3367.93 g/mol means the non-DAC peptide, and given the price gap between the two products that substitution should be checked, not presumed. A mass 18 Da higher than expected reveals that the maleimide ring has hydrolysed to maleamic acid, which can no longer bind albumin even though it still binds the receptor — a degradation product that the purity percentage will not expose. Otherwise follow standard practice: look for a single symmetrical peak in the chromatogram, confirm that the lot number agrees with the vial, and compare net peptide content with gross weight, as explained in our COA reading guide.
Regulatory position
No CJC-1295 product, with or without DAC, is authorised as a medicine in the United States, the EU or anywhere else; the original development programme stopped short of approval. It is not a food supplement ingredient and not a routinely available compounded medicine. Our material is for laboratory research only and not for human consumption.
Related compounds and further reading
The non-DAC form is the direct structural twin and the correct comparator for any experiment that isolates exposure duration. Sermorelin is the unmodified parent fragment, and tesamorelin the acylated full-length analogue. On the secretagogue side, ipamorelin and the GHRPs act at the ghrelin receptor rather than the GHRH receptor; the full landscape is laid out in the GH secretagogue landscape explained.
Questions
What does "DAC" mean in CJC-1295 with DAC?
DAC stands for drug affinity complex: a maleimidopropionyl group attached to an extra lysine at position 30, outside the 1 to 29 receptor-binding sequence. The maleimide undergoes Michael addition with the free cysteine-34 thiol on serum albumin, creating a stable covalent thioether bond that anchors the peptide to a long-lived carrier protein.
Why does binding to albumin lengthen the half-life so dramatically?
Albumin is the most abundant protein in plasma and remains in circulation for about three weeks. Once covalently attached, the peptide is too large for renal filtration and largely protected from peptidases, so it is cleared at the rate of albumin turnover rather than peptide turnover. Animal studies and early human pharmacokinetic work reported half-lives of several days.
What distinguishes CJC-1295 with DAC from the version without DAC?
Both share the Modified GRF 1-29 backbone and act through the same receptor mechanism. The DAC form adds a lysine at position 30 carrying the maleimide linker, increasing the mass from 3367.93 to 3647.28 g/mol. Functionally, the difference is the exposure profile: a plateau lasting days instead of a pulse lasting well under an hour.
In which studies is the DAC version the right choice?
It fits studies that need continuous GHRH receptor occupancy — examining how sustained agonist exposure affects somatotroph signalling, receptor expression, desensitisation and downstream IGF-1. For questions about pulsatile physiology or discrete receptor activation, the short-acting non-DAC version is the appropriate tool. This is a design decision, not a matter of preference.
Can the maleimide react with things other than albumin?
Yes — and that is the chief handling risk. Maleimides react with any accessible thiol, so reducing agents such as dithiothreitol or beta-mercaptoethanol, as well as free cysteine or thiol-containing media supplements, will consume the linker. Use a thiol-free diluent near neutral pH and avoid leaving the peptide in solution for long periods.
What is maleamic acid, and why should researchers care?
Maleamic acid is what forms when the maleimide ring hydrolyses, which happens slowly in aqueous solution and more quickly at alkaline pH. It shows up on a mass spectrum 18 Da above the expected mass. The hydrolysed peptide still binds the GHRH receptor but can no longer attach to albumin, so it loses its long-acting behaviour — something the purity percentage will not reveal.
Which check on a CJC-1295 with DAC certificate matters most?
The measured mass, which should be 3647.28 g/mol. A value near 3367.93 g/mol indicates the non-DAC peptide, a considerably cheaper product, so this possible substitution should be verified rather than assumed. A mass 18 Da above the expected figure points to a hydrolysed maleimide that cannot conjugate.
Is CJC-1295 with DAC approved as a medicine?
No. Its original development programme did not reach approval, and no CJC-1295 product has marketing authorisation in the United States or any other country. It is neither a food supplement ingredient nor a generally available compounded medicine.