CJC 1295 without DAC, also known as modified GRF(1-29) or mod GRF 1-29, is a synthetic, 29-residue analogue of growth hormone-releasing hormone (GHRH). Four amino acid substitutions make it more resistant to enzymatic and chemical breakdown than the native fragment, and it lacks the albumin-binding linker found in the DAC version. It is studied in vitro as a selective agonist of the GHRH receptor on pituitary somatotroph cells, where it is used to examine cAMP signalling and growth hormone release. This article covers its structure, mechanism, published research, laboratory applications and handling requirements.
What is CJC 1295 without DAC?
CJC 1295 without DAC is a tetrasubstituted version of GHRH(1-29), the shortest fragment of human GHRH that retains full biological activity at the GHRH receptor. Native GHRH is a 44-residue hypothalamic peptide. It was characterised in 1982, when independent groups, including those led by Roger Guillemin and Jean Rivier, isolated and sequenced it from pancreatic tumours associated with acromegaly. Structure-activity work then established that the N-terminal 29 residues carry the receptor-binding and activating determinants.
The native 1-29 fragment is short-lived because plasma dipeptidyl peptidase-IV (DPP-IV) cleaves it at the N-terminus, and several residues are chemically labile. The modified sequence addresses this with four substitutions: D-alanine replaces alanine at position 2, glutamine replaces asparagine at position 8, alanine replaces glycine at position 15, and leucine replaces methionine at position 27. The sequence is Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2, with an amidated C-terminus. The theoretical molecular weight is approximately 3,368 Da, corresponding to the formula C152H252N44O42.
Each substitution has a rationale. The D-alanine blocks DPP-IV recognition. Replacing asparagine removes a site prone to deamidation. The alanine at position 15 is thought to stabilise the helical conformation, and replacing methionine eliminates a residue vulnerable to oxidation.
Terminology causes real confusion. “CJC-1295” originally described a compound that carried a maleimide-based drug affinity complex (DAC) for covalent albumin binding, and the “without DAC” product is chemically the modified GRF(1-29) peptide alone. Suppliers use “CJC-1295 no DAC”, “CJC 1295 without DAC” and “mod GRF 1-29” for the same material, so a certificate of analysis should state the sequence and expected mass explicitly.
Mechanism of action
The peptide acts on the GHRH receptor (GHRHR), a class B G protein-coupled receptor expressed on anterior pituitary somatotrophs. Binding of the N-terminal region of the ligand to the transmembrane core, together with engagement of the receptor’s extracellular domain by the helical C-terminal portion, triggers a conformational change that activates the stimulatory G protein, Gs.
Gs activation stimulates adenylyl cyclase, raising intracellular cyclic AMP. This activates protein kinase A, which phosphorylates the transcription factor CREB and promotes both growth hormone gene transcription and the exocytosis of stored hormone. Elevated cAMP also raises calcium influx through voltage-gated channels, contributing to granule release. In cell culture, these steps are readily measured through cAMP accumulation assays, CREB phosphorylation and growth hormone concentrations in the medium.
Native GHRH release in vivo is pulsatile, and growth hormone secretion is constrained by somatostatin, which acts as a counterbalancing inhibitory signal. A GHRH analogue acts upstream of growth hormone itself, so the pituitary’s own regulatory machinery remains part of the system in whole-animal work. This distinguishes it from direct administration of recombinant growth hormone, where that physiological layer is bypassed.
The lack of the DAC linker has a defined consequence. The peptide does not covalently bind serum albumin, so its plasma persistence is far shorter than that of the conjugated form. Published pharmacological descriptions place its half-life at roughly half an hour, although values vary with species and conditions. For researchers, this means that receptor occupancy in experiments is brief and tightly tied to exposure time. Short-pulse stimulation designs are therefore easy to model with this compound, in contrast to experiments intended to produce sustained receptor activation.
Unlike growth hormone secretagogue receptor agonists such as ghrelin mimetics, the peptide does not act through the ghrelin receptor. It is mechanistically separate from the growth hormone releasing peptide family.
What the research shows
The published literature on this exact peptide is thinner than the literature on its albumin-conjugated relative, so it helps to distinguish what was tested on which molecule.
The foundational preclinical paper is Jetté and colleagues’ 2005 study in Endocrinology. The team synthesised maleimido derivatives of hGRF(1-29), bioconjugated them to human serum albumin, and tested them in cultured rat anterior pituitary cells and in rats. All three conjugates showed greater resistance to DPP-IV in vitro and were active in a growth hormone secretion assay. The lead compound, CJC-1295, produced a roughly four-fold increase in growth hormone area under the curve over two hours compared with unmodified hGRF(1-29), and remained detectable in plasma beyond 72 hours. Its relevance here is that the compound’s peptide backbone is the same tetrasubstituted GRF(1-29) sequence, so the paper explains the design logic behind the substitutions. It is indexed on PubMed.
A second study used a genetic model. Alba and colleagues reported in the American Journal of Physiology: Endocrinology and Metabolism in 2006 that once-daily administration of the DAC-containing analogue normalised growth in the GHRH knockout mouse, a strain in which the GHRH signal is absent. The finding indicated that the analogue was a functional agonist of the receptor in vivo, restoring growth hormone axis activity in animals lacking endogenous GHRH. The record is on PubMed.
A third body of work concerns the degradation of native GRF. Earlier enzymology studies established that plasma rapidly cleaves the N-terminal dipeptide from GHRH, yielding an inactive product, and this finding motivated the D-amino acid substitution at position 2. Researchers who want to understand why unmodified GRF(1-29) performs poorly in plasma-containing assays should consult that literature on DPP-IV-mediated inactivation.
A fourth area is receptor pharmacology in primary pituitary cultures and cell lines transfected with GHRHR. These systems have been used to compare GRF analogues by potency and efficacy in cAMP generation and growth hormone release, and to study cross-talk with somatostatin signalling. Study designs and reported values vary considerably between laboratories, so readers should check the original methods before comparing numbers across papers.
Research applications
The peptide is used in several in-vitro contexts. The most common is receptor pharmacology, in which cell lines expressing GHRHR are stimulated with defined concentrations of the peptide and cAMP, PKA activity or reporter-gene output is measured. Dose-response curves generated with a stabilised analogue are cleaner than those from native GRF(1-29), because less of the compound is lost to degradation during the incubation.
Primary pituitary cell culture is a second application. Dispersed rodent pituitary cells respond to GHRH agonists with growth hormone release, giving a functional readout that sits closer to physiology than a transfected line. Co-treatment with somatostatin or its analogues allows the interaction between the stimulatory and inhibitory arms of the axis to be examined.
The peptide also serves in comparative studies of GHRH analogues, as a reference agonist when screening new antagonists or modified peptides, and in analytical method development. Its short, well-defined sequence makes it a convenient standard for reversed-phase HPLC, mass spectrometry and peptide mapping, and for studying how single-residue substitutions affect stability. Stability-indicating assays are a further use, since the substitutions at positions 8 and 27 allow degradation by deamidation and oxidation to be compared directly against the native sequence.
Purity, storage and handling
Verification starts with reversed-phase HPLC, typically at 214 or 220 nm, with purity commonly specified at 98% or higher by peak area. A single HPLC trace is not sufficient on its own. Mass spectrometry should confirm that the observed mass matches the theoretical figure of about 3,368 Da, which also rules out confusion with the DAC-conjugated product. Net peptide content is a separate matter, because lyophilised peptides contain counter-ions, usually trifluoroacetate, and bound water. The gross weight in the vial therefore overstates the amount of active peptide, which affects molar calculations in quantitative assays.
Because degradation accelerates once reconstituted, batch-level HPLC verification matters more here than with more stable peptides. UK laboratories sourcing CJC 1295 Without Dac should expect a batch-specific certificate of analysis and lyophilised storage at -20°C, and anyone comparing the best peptides supplier uk options can use those documentation standards as a practical checklist when assessing any vendor.
A batch-specific certificate matters because synthesis yield, impurity profile and counter-ion content differ between production runs. Deletion sequences and truncated products from solid-phase synthesis can co-elute with the main peak if the gradient is poorly optimised, so the method conditions should be stated. The certificate should carry a batch number matching the vial, the test date and the analytical methods used.
Lyophilised peptide is normally kept at -20°C in a sealed, desiccated container, and vials should reach room temperature before opening so that condensation does not add moisture. Short-term transit at ambient temperature is generally tolerated by dry material, but prolonged warm storage is not recommended. Once reconstituted, peptides in solution are far more vulnerable to hydrolysis, aggregation and adsorption to plastic surfaces. Reconstituted solutions are usually held at 2-8°C for limited periods, and dividing the stock into single-use aliquots avoids repeated freeze-thaw cycles. The substitutions in this sequence reduce two common degradation routes, deamidation at position 8 and methionine oxidation at position 27, but they do not remove hydrolytic or aggregation risk. Exact stability windows depend on the diluent, pH and concentration, so they should be taken from supplier data and verified in-house for critical work.
Light sensitivity is modest, since the sequence contains tyrosine and phenylalanine but no tryptophan. Even so, amber vials or storage in the dark remain sensible practice, particularly for solutions held over several days.
Frequently asked questions
Is CJC-1295 without DAC the same as mod GRF 1-29?
Yes, in practice. Both names describe the tetrasubstituted 29-residue GHRH analogue that lacks the drug affinity complex linker. The “CJC-1295” label originally referred to the DAC-containing compound, so researchers should check the certificate of analysis for sequence and mass to avoid confusing the two products.
What is the molecular weight of CJC-1295 without DAC?
The theoretical molecular weight is approximately 3,368 Da, with the formula C152H252N44O42 for the amidated free peptide. The DAC-containing version is heavier because of the added linker. Mass spectrometry on each batch should agree with the theoretical value within normal instrument tolerance.
How should lyophilised CJC 1295 without DAC be stored?
Lyophilised material is typically stored at -20°C in a sealed, desiccated container protected from light. Vials should reach room temperature before opening to prevent condensation. Reconstituted solutions are generally held at 2-8°C for short periods as single-use aliquots, with exact limits taken from batch documentation.
Which receptor does CJC-1295 without DAC act on?
It is an agonist at the GHRH receptor on pituitary somatotrophs, a class B G protein-coupled receptor that signals through Gs to raise cAMP and activate PKA. It does not act on the ghrelin receptor, so its mechanism differs from that of growth hormone releasing peptides such as ipamorelin.
This compound is supplied for in-vitro laboratory research only. It is not for human or veterinary use, and it must not be administered to people or animals.
