Quick answer
CJC-1295 with DAC is a stabilized GHRH(1-29) analog carrying a maleimide drug affinity complex that bonds covalently to serum albumin, extending its persistence in animal models from minutes to days while leaving GHRH-receptor pharmacology unchanged.
- Mass: about 3,647 Da, versus about 3,368 Da for the no-DAC form
- Mechanism: GHRH receptor, Gs, cAMP, GH synthesis and release
- Handling: avoid thiol-containing additives; keep the lyophilized cake cold and dry; use the calculator for mg/mL math
- Availability: V8 stocks CJC-1295 (No DAC) rather than the DAC form
- Status: For laboratory research use only; not for human consumption.
CJC-1295 with DAC is a synthetic analog of growth-hormone-releasing hormone (GHRH) that carries a drug affinity complex, a maleimide-bearing group that bonds covalently to serum albumin. This guide collects what is established about its structure, mechanism, preclinical behavior and laboratory handling. For laboratory research use only; not for human consumption. V8 Peptides does not currently stock the DAC form; the closely related CJC-1295 (No DAC) is available for comparison work.
What CJC-1295 with DAC is
CJC-1295 with DAC is a 29-residue peptide, plus one added lysine, built on the first 29 amino acids of human GHRH, the shortest fragment that keeps full receptor-activating potency. Four residue substitutions protect the backbone from proteases, and an added C-terminal lysine carries a maleimidopropionyl group. The maleimide reacts with the free thiol of cysteine-34 on serum albumin, so in biological systems the peptide circulates largely as an albumin conjugate. Albumin turns over slowly and is not filtered by the kidney, which is why the research half-life of the DAC form is measured in days, whereas the no-DAC analog is cleared within minutes.
The key conceptual point is that DAC changes how long the peptide is available, not which receptor it activates. The receptor-facing portion is the same as in the no-DAC analog, and the GHRH receptor pharmacology is shared with sermorelin. This makes the DAC form a tool for questions about sustained rather than pulsatile receptor availability.
| Property | CJC-1295 with DAC | CJC-1295 (No DAC) |
|---|---|---|
| Backbone | Tetrasubstituted GHRH(1-29) | Same tetrasubstituted GHRH(1-29) |
| Extra group | C-terminal lysine with maleimidopropionyl linker | None |
| Approximate mass | about 3,647 Da | about 3,368 Da |
| Albumin coupling | Covalent, via cysteine-34 thiol | No dedicated coupling group |
| Persistence in animal models | Days | Minutes |
| Typical experimental use | Sustained-exposure and time-course studies | Pulse, onset and decay studies |
Discovery and history
GHRH itself was isolated in 1982, when two groups purified it from pancreatic tumors that had caused acromegaly (Guillemin and colleagues; Rivier and colleagues). The 44-residue hormone proved to have a short life in plasma: dipeptidyl peptidase IV removes the N-terminal Tyr-Ala dipeptide, and the product is biologically inactive (Frohman et al., 1986). Native GHRH is therefore cleared within minutes, and shorter fragments such as GHRH(1-29), later known as sermorelin, share that limitation.
Chemists attacked the problem in two stages. The first was backbone armor: substituting residues at the positions that proteases and oxidation attack, producing the modified GRF(1-29) sequence. The second was carrier engineering. Researchers at ConjuChem, a Canadian biotechnology company (the origin of the "CJC" prefix), attached a reactive maleimide group so the analog would bind albumin after entering plasma. Jetté and colleagues described these GRF-albumin bioconjugates in 2005 and identified CJC-1295 as a long-lasting analog in rats. A subsequent clinical-pharmacology report in healthy adults (Teichman et al., 2006) described GH concentrations that stayed elevated for roughly a week and IGF-I elevations lasting longer, with a half-life of several days, which confirmed in a published dataset that the albumin strategy worked as designed.
The naming has caused lasting confusion. "CJC-1295" is used both for the DAC-bearing molecule and, informally, for the shorter modified GRF(1-29) without DAC. The two are not interchangeable reagents; this ambiguity is why a structural description should accompany the name in any methods section. The side-by-side logic is developed in the DAC versus no-DAC research comparison and in the shorter discovery and history note.
Chemical structure and synthesis
The GHRH(1-29) core and its substitutions
Native GHRH(1-29)-amide reads YADAIFTNSYRKVLGQLSARKLLQDIMSR. In the CJC-1295 backbone four positions are changed: L-alanine at position 2 becomes D-alanine, which blocks dipeptidyl peptidase-4 cleavage at the Tyr1-Ala2 bond; asparagine 8 becomes glutamine; glycine 15 becomes alanine; and methionine 27 becomes leucine, which removes the oxidation-prone thioether. These changes are shared with the no-DAC molecule, as described in the no-DAC structure article.
The DAC linker
The drug affinity complex is a maleimidopropionic acid unit attached to the side chain of an added C-terminal lysine. Maleimides are Michael acceptors that react selectively with free thiols at near-neutral pH. In plasma, the single unpaired cysteine of albumin (Cys34) is the dominant free thiol, so the conjugation is highly selective. The resulting thioether bond is stable, which is what makes the half-life extension durable rather than an equilibrium binding effect.
Solid-phase assembly and purification
Like most peptides of this size, the molecule is assembled by solid-phase peptide synthesis, coupling protected amino acids to a resin-bound chain one residue at a time. After cleavage and side-chain deprotection the crude product is purified by preparative reverse-phase HPLC and then lyophilized (see what is lyophilization). Sequence conventions are explained in understanding amino acid sequences; the full chemistry is also in the structure and synthesis article.
Analytical challenges unique to the DAC form
A reactive maleimide complicates characterization. Hydrolysis opens the maleimide ring and produces a species with the correct peptide sequence that can no longer couple to albumin; a reaction with any thiol in a buffer or sample additive consumes the linker without changing the backbone. A single purity percentage therefore does not prove that the affinity complex is intact. Orthogonal methods are used: chromatography resolves the major components, mass spectrometry confirms a mass near 3,647 Da, and the ring-opened product appears as a species about 18 Da heavier from water addition.
Mechanism of action
Receptor engagement
The GHRH receptor is a class B G-protein-coupled receptor on pituitary somatotrophs. Ligand binding activates Gs, stimulates adenylate cyclase and raises intracellular cAMP; protein kinase A signaling then promotes transcription of the GH gene and the release of stored growth hormone. CJC-1295 with DAC engages this pathway in the same way as native GHRH, and the substitutions make the ligand durable enough to maintain the signal. The mechanism of action article develops this in more depth.
Albumin binding as a pharmacokinetic, not pharmacodynamic, feature
Albumin conjugation is not a second signaling mechanism. It alters distribution and clearance while the GHRH-facing domain supplies receptor selectivity. In protein-containing experimental systems, investigators must distinguish free peptide, albumin-bound peptide and total peptide. Albumin concentration, thiol availability and incubation time all affect how much conjugation occurs, so two media with the same nominal peptide concentration can present different receptor exposures.
Sustained versus pulsatile signaling
Endogenous GHRH reaches the pituitary in bursts, and the GH axis is sensitive to signal timing. Ionescu and Frohman (2006) examined this question directly with CJC-1295 and reported that pulsatile GH secretion persisted during continuous stimulation, while the baseline between pulses rose. That result indicates that a sustained GHRH-receptor signal does not simply flatten secretion; it raises the floor and leaves a pulse structure that is still governed by somatostatin and other inputs. For the receptor-level comparison with the short-acting analog and sermorelin, see the sermorelin mechanism article.
Downstream axis
Raised GH output stimulates hepatic IGF-I production, and IGF-I feeds back on both the pituitary and the hypothalamus. Because IGF-I responds more slowly than GH, it integrates exposure over time and is a useful readout for sustained-exposure designs.
Preclinical research findings
The published record for this compound is small but specific. The table below lists the systems and findings that can be stated with confidence; broader context is in the preclinical research article.
| Model or system | Question | Reported finding | Source |
|---|---|---|---|
| Rat, GRF-albumin bioconjugates | Does albumin coupling extend GRF activity? | Conjugates activated the GRF receptor and produced a much longer GH-releasing effect than unconjugated GRF(1-29); CJC-1295 identified as the long-lasting analog | Jetté et al., 2005 |
| GHRH knockout mouse | Can the analog restore GHRH-dependent growth? | Once-daily exposure restored growth parameters toward normal in animals lacking endogenous GHRH | Alba et al., 2006 |
| Clinical-pharmacology study, healthy adults | How long do GH and IGF-I stay raised? | GH elevated for about a week or more, IGF-I for longer; half-life of several days | Teichman et al., 2006 |
| Frequent-sampling study, healthy adults | Does sustained stimulation abolish pulsatility? | Pulses persisted on a raised baseline | Ionescu and Frohman, 2006 |
Reading these findings
The persistent theme is pharmacokinetic. The papers establish that albumin coupling lengthens exposure and that the GH axis responds with sustained but still pulsatile secretion. They do not establish that longer exposure is better for any outcome, and they do not describe the product sold by any vendor. Good designs separate the contribution of the backbone from that of the carrier by comparing DAC and no-DAC analogs, characterizing binding in albumin-containing and albumin-limited media, and sampling at early and late time points. Vehicle controls, matched analytical purity and confirmation that the maleimide is intact keep reagent degradation from being mistaken for biology. Reporting both absolute and normalized readouts clarifies whether apparent persistence reflects altered exposure or altered tissue responsiveness. These are controlled-system observations only.
Handling, reconstitution and storage
CJC-1295 with DAC is supplied as a lyophilized cake. Two handling points follow from the chemistry. First, avoid diluents or additives that contain free thiols (dithiothreitol, mercaptoethanol, cysteine), because they react with the maleimide. Second, moisture accelerates ring-opening hydrolysis, so the sealed vial should stay cold, dry and dark until needed. Reconstitution technique is otherwise standard: bring the vial to room temperature, add bacteriostatic water slowly down the inside wall, and swirl without vortexing. The general procedure is in the lyophilized-peptide reconstitution guide, the DAC-specific notes are in CJC-1295 (DAC) reconstitution and storage, and the worked step-by-step example for another peptide is how to reconstitute retatrutide. The reconstitution calculator performs the arithmetic.
The governing relation is concentration (mg/mL) = peptide mass (mg) ÷ diluent volume (mL). Molar equivalents for in-vitro planning use a molecular weight of about 3,647 g/mol.
| Vial contents | Diluent added | Concentration | Approx. molarity |
|---|---|---|---|
| 2 mg | 1 mL | 2 mg/mL | about 548 µM |
| 2 mg | 2 mL | 1 mg/mL | about 274 µM |
| 5 mg | 2 mL | 2.5 mg/mL | about 685 µM |
| 5 mg | 1 mL | 5 mg/mL | about 1,371 µM |
These figures assume the labeled mass is entirely peptide; for exact molar work, correct for net peptide content on the lot certificate. Lyophilized powder is the most stable form. Once in solution, the linker is the weak point, so solutions should not be held for long periods, and single-use aliquots in low-bind tubes limit freeze-thaw cycling. The 28-day figure often cited for refrigerated bacteriostatic solutions is a multi-use container convention, not measured stability data for this molecule. General cold-chain principles are in storing research peptides.
Purity, COA and quality
For a maleimide-bearing peptide, quality documentation matters more than usual. A usable certificate of analysis reports chromatographic purity with the actual trace, a mass-spectrometry identity near the expected 3,647 Da, and the batch number that matches the vial. The characteristic impurities of DAC material are the ring-opened maleimide species and deletion sequences from stepwise synthesis. Review the chromatogram, not only the summary figure, and log batch and storage history with each dataset so lot-to-lot differences are not mistaken for biological variability. The COA page shows example batch documents for stocked compounds, CJC-1295 (DAC) purity testing covers the impurity profile, and the primers how to read a COA and understanding HPLC purity explain the methods.
Related compounds and comparisons
Three neighbours help place the DAC analog. The DAC versus no-DAC comparison isolates the carrier effect. Sermorelin is the unmodified GHRH(1-29) baseline, and tesamorelin is a stabilized full-length GHRH analog with a different modification strategy. On the secretagogue side, ipamorelin acts at the ghrelin receptor rather than the GHRH receptor, and the two pathways are often examined together (see CJC-1295 vs ipamorelin).
| Analog | Receptor | Persistence strategy | Relative duration in models |
|---|---|---|---|
| Sermorelin | GHRH receptor | None (native 1-29 sequence) | Shortest |
| CJC-1295 (No DAC) | GHRH receptor | Four protease-resistance substitutions | Short, pulse-like |
| CJC-1295 with DAC | GHRH receptor | Substitutions plus covalent albumin binding | Days |
| Tesamorelin | GHRH receptor | Modified full-length sequence | Intermediate |
| Ipamorelin | Ghrelin (GHS-R1a) receptor | Short pentapeptide with non-natural residues | Short |
Researchers who need the shorter-acting backbone can source CJC-1295 (No DAC); the sourcing guide lists what to check, and the CJC-1295 (No DAC) + ipamorelin blend covers the paired design.
Frequently asked questions
What does DAC stand for and what does it do?
DAC is the drug affinity complex, a maleimidopropionyl group on an added C-terminal lysine. It reacts with the free thiol of albumin cysteine-34 and tethers the peptide to a long-lived carrier, extending its persistence in animal models from minutes to days.
Does DAC change which receptor the peptide activates?
No. The receptor-binding domain is the same modified GHRH(1-29) used in the no-DAC form. DAC alters clearance and distribution, not receptor selectivity or the cAMP signaling cascade.
What is the approximate molecular weight?
About 3,647 Da for the intact DAC peptide, roughly 280 Da more than the no-DAC form at about 3,368 Da. Mass spectrometry resolves the difference easily.
What are the four backbone substitutions?
D-alanine at position 2 (blocks dipeptidyl peptidase-4), glutamine at position 8, alanine at position 15 and leucine at position 27, which replaces an oxidation-prone methionine.
What is the main stability concern for DAC material?
Hydrolysis of the maleimide ring. A ring-opened molecule keeps its GHRH-receptor activity but can no longer couple to albumin, so it behaves like a short-acting analog. Cold, dry storage limits this.
Why avoid thiol-containing reagents?
Free thiols from reducing agents or cysteine-containing additives react with the maleimide and consume the linker, changing the chemical species without altering the peptide sequence.
Is CJC-1295 with DAC the same as modified GRF(1-29)?
No. Modified GRF(1-29) is the backbone without DAC. The names are sometimes used loosely, which is why a methods section should state whether the affinity complex is present.
What does a sustained signal do to GH pulsatility?
In the Ionescu and Frohman study, pulses persisted during continuous stimulation while the baseline between pulses rose. Sustained receptor availability did not eliminate pulse structure.
Does V8 Peptides carry the DAC form?
No. The DAC form is not currently carried. The CJC-1295 (No DAC) product is the nearest available reagent for comparison designs.
What documentation should accompany a lot?
A lot-specific certificate of analysis showing the HPLC trace, a mass value near 3,647 Da and a batch number matching the vial. See how to read a COA.
Research Use Only. For laboratory research use only; not for human consumption. Not for veterinary, clinical, or diagnostic purposes. This guide is research education, not usage guidance.
References
- Jetté L, Léger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058.
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805.
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797.
- Alba M, Fintini D, Sagazio AM, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-E1294.
- Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the Tyr1-Ala2 bond. J Clin Invest. 1986;78(4):906-913.
- Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585-587.
- Rivier J, Spiess J, Thorner M, Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982;300(5889):276-278.
Lot-testing details for this compound class: CJC-1295 DAC purity testing.