CJC-1295 (DAC and no-DAC): a GHRH analogue in two forms

CJC-1295 is a synthetic analogue of growth hormone-releasing hormone (GHRH), built on the first 29 residues of the native hormone, the fragment known as GRF(1-29). It reaches laboratories in two closely related builds that share the same core sequence but differ sharply in how long they persist in a studied system. Both act as agonists at the GHRH receptor found on pituitary somatotrophs, the cells responsible for producing growth hormone. Researchers reach for these molecules when they want a stable, well-characterised GHRH-receptor probe rather than the rapidly degraded native peptide, which enzymes clear within minutes.

The first build is modified GRF(1-29), often labelled CJC-1295 without DAC. It is a 29-residue chain carrying targeted substitutions: a D-alanine at position 2, plus glutamine, alanine, and leucine swaps at positions 8, 15, and 27, finished with a C-terminal amide. Those changes exist for one reason, to slow the enzymatic breakdown that clears the native peptide almost immediately. Strip away any linker chemistry and this is the plain GHRH-receptor agonist, valued in receptor-signalling work for its short, predictable presence.

The second build is CJC-1295 with DAC, sometimes written DAC:GRF. It keeps the same modified GRF(1-29) backbone and then adds a drug-affinity-complex linker, a maleimidopropionyl-lysine group appended at position 30. That group reacts with a free thiol on circulating serum albumin, forming a covalent bond that tethers the peptide to a large carrier protein. Bound to albumin, the molecule resists filtration and enzymatic clearance for far longer, which is the entire point of the DAC design. Where the no-DAC form gives a brief pulse of receptor activity, the DAC form sustains a signal across a much longer window in studied systems.

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A shared backbone, two lifespans

Both forms begin from the identical amino-acid sequence, YADAIFTQSYRKVLAQLSARKLLQDILSR. Read left to right, that string is the modified GRF(1-29) scaffold, and it is what lets either molecule dock into the GHRH receptor and trigger the same downstream cascade: activation of the receptor, a rise in intracellular cyclic AMP, and stimulation of the somatotroph. The substitutions relative to native GRF(1-29) matter because the native sequence is a prime target for the enzyme dipeptidyl peptidase-4, which snips it near the N-terminus. Swapping in a D-alanine at position 2 blunts that cut, and the remaining substitutions further stiffen the chain against degradation. The result is a peptide that keeps the biological grammar of GHRH while shedding its fragility.

The drug-affinity-complex difference

The linker is what separates the two products at the molecular level. In the no-DAC build the chain simply ends, so the molecule circulates as a free peptide and is cleared on the order of minutes to a few hours in studied systems. In the DAC build the added maleimide group finds a cysteine thiol on albumin and locks on. Albumin is one of the most abundant and longest-lived proteins in blood, so hitching a ride on it stretches the effective presence of the peptide into a span measured in days rather than minutes. Ionescu and Frohman documented exactly this behaviour: continuous exposure to the DAC form produced a sustained rise in growth-hormone output while the natural pulsatile rhythm of secretion was preserved, a finding that reframed how a long-acting GHRH analogue behaves at the pituitary. The contrast is stark: the free peptide is a brief spark, while the albumin-bound version is a slow, steady glow that holds receptor tone in place across many hours.

The albumin-tethering mechanism itself was worked out earlier by Jette and colleagues, who showed that GRF(1-29) bioconjugates built on this drug-affinity-complex chemistry could bind albumin and still activate the GHRH receptor on the anterior pituitary in rodent models. That work established the design principle the DAC form relies on: attach a small reactive group, let the body's own albumin become the carrier, and gain a dramatically longer functional presence without redesigning the active sequence. It is an elegant trick, and it is the single feature that sets the DAC molecule apart from its no-DAC sibling.

Why researchers keep both

The practical reason to stock both is temporal resolution. A study that needs a sharp, transient GHRH-receptor stimulus, for example mapping the immediate signalling response of somatotrophs, favours the no-DAC form because its brief presence keeps the experimental window clean. A study that needs steady receptor engagement across days, such as observing adaptive changes in a cell or tissue model under prolonged GHRH tone, favours the DAC form. Neither is a better molecule in the abstract; they are two tools calibrated to different timescales, and choosing between them is really a question about the length of the signal you want to observe. Both are supplied as lyophilised powders and reconstituted in the laboratory before use in receptor assays. In practice, comparing the two side by side within a single experimental design is one of the cleanest ways to isolate the effect of half-life alone, since the active sequence and receptor target are held constant while only the persistence of the signal changes.

Molecular identity

The verified molecular records for each form are listed below.

• CJC-1295 without DAC (modified GRF 1-29): molecular formula C152H252N44O42, molecular weight 3367.9 g/mol, sequence YADAIFTQSYRKVLAQLSARKLLQDILSR with a C-terminal amide.
• CJC-1295 with DAC (DAC:GRF): molecular formula C165H269N47O46, molecular weight 3647.2 g/mol, CAS 446262-90-4, same core sequence plus a lysine-linked albumin-binding drug-affinity complex.

Common questions

What is the difference between CJC-1295 with and without DAC?

Both share the modified GRF(1-29) sequence and both act as GHRH-receptor agonists. The DAC version adds a maleimidopropionyl-lysine group that binds covalently to serum albumin, which extends how long the molecule persists in a studied system. The no-DAC version has no such linker, so it is cleared far faster. Behaviour at the receptor is the same; the difference is duration.

Is CJC-1295 the same as modified GRF(1-29)?

In common usage, yes. CJC-1295 without DAC and modified GRF(1-29) name the same 29-residue analogue, with a D-alanine at position 2 and substitutions at positions 8, 15, and 27. The label CJC-1295 with DAC then refers to that same backbone carrying the added drug-affinity-complex linker at position 30.

What is CJC-1295 studied for?

It serves as a stable probe of GHRH-receptor signalling in laboratory settings. Because the native GRF(1-29) peptide degrades quickly, the modified and DAC-bearing versions give researchers a reproducible way to engage the receptor and observe downstream responses over defined timescales. All such work is confined to controlled research contexts and is not intended for use in people or animals.

References

1. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone persists during continuous stimulation by CJC-1295, a long-acting growth hormone-releasing hormone analog. Journal of Clinical Endocrinology and Metabolism. 2006;91(12):4792-4797.
2. Jette L, Leger 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. Endocrinology. 2005;146(7):3052-3058.