CJC-1295 With DAC vs Without DAC: What Is the Difference?

Quick answer: CJC-1295 with DAC and CJC-1295 without DAC share the same modified GHRH(1-29) backbone. The difference is a single added lysine carrying a reactive maleimide group, the Drug Affinity Complex (DAC), which bonds covalently to serum albumin and extends the peptide's persistence from roughly half an hour to several days in published pharmacokinetic work. The no-DAC form, also called Modified GRF (1-29), produces a brief, pulse-like stimulus at the GHRH receptor; the DAC form produces a prolonged one.

This article compares the two at the level of chemistry, receptor pharmacology and bench handling. For laboratory research use only; not for human consumption.

What is CJC-1295?

Growth hormone-releasing hormone (GHRH) is a 44-residue hypothalamic peptide. Its first 29 residues, GHRH(1-29), retain full activity at the GHRH receptor on pituitary somatotrophs; that fragment is known as sermorelin. The limitation of the native fragment as a research tool is stability: dipeptidyl peptidase-IV (DPP-IV) cleaves it after the alanine at position 2 within minutes, and several other residues are prone to chemical degradation.

CJC-1295 was developed in the early 2000s to address that. Its backbone is GHRH(1-29) with four amino acid substitutions, and in its original form it also carries the DAC group. Over time the name came to be used for two distinct molecules:

• CJC-1295 with DAC – the tetrasubstituted peptide plus a C-terminal lysine linked to maleimidopropionic acid. This is the compound described in the original literature.
• CJC-1295 without DAC – the tetrasubstituted 29-residue peptide alone, more precisely called Modified GRF (1-29) or Mod GRF 1-29.

CJC-1295 with DAC vs without DAC at a glance

The shared backbone: four substitutions

Each of the four changes to the native GHRH(1-29) sequence addresses a specific weakness:

• D-Ala at position 2 replaces L-alanine. DPP-IV cannot efficiently cleave after a D-amino acid, which removes the main route of rapid enzymatic inactivation.
• Gln at position 8 replaces asparagine. Asparagine residues deamidate readily; glutamine is far more resistant, improving chemical stability.
• Ala at position 15 replaces glycine, a change associated with improved receptor activity in structure–activity studies of GHRH analogs.
• Leu at position 27 replaces methionine, eliminating a residue that oxidizes easily during storage and handling.

Together these substitutions raise the persistence of the peptide from under ten minutes for unmodified GHRH(1-29) to roughly thirty minutes for Mod GRF 1-29. That is a meaningful gain, but the peptide is still small enough to be filtered rapidly by the kidney.

What the DAC group adds

The Drug Affinity Complex is a chemistry platform, not a peptide sequence. In CJC-1295, a lysine is appended to the C-terminus and its side-chain amine is acylated with maleimidopropionic acid. Maleimides react selectively with free thiols. Serum albumin has exactly one free thiol, at cysteine 34, and it is abundant in plasma. Once the peptide encounters albumin, a stable thioether bond forms and the peptide becomes, in effect, a small appendage on a 66 kDa protein.

That bioconjugation changes the peptide's fate in three ways:

• The conjugate is far too large for renal filtration.
• Albumin shields the peptide sterically from circulating proteases.
• The conjugate inherits albumin's long circulating residence, which is maintained by FcRn-mediated recycling.

The original preclinical paper (Jetté and colleagues, 2005) screened several GHRH(1-29)–albumin bioconjugates in rats and identified CJC-1295 as the candidate that retained activity at the pituitary GHRH receptor after conjugation. Later pharmacokinetic work reported an elimination half-life of about six to eight days, with elevated growth hormone and IGF-1 measurements lasting well beyond a single administration.

Pulsatile versus sustained receptor exposure

Growth hormone is released from the pituitary in discrete pulses, shaped by the interplay of GHRH, somatostatin and ghrelin signaling. The two CJC-1295 forms interact with that rhythm differently, which is the main reason a study might call for one rather than the other.

Without DAC

Mod GRF 1-29 delivers a short stimulus. Receptor occupancy rises and falls within a window comparable to an endogenous GHRH pulse. In experimental designs it is often paired with a ghrelin-receptor agonist, because GHRH-receptor and GHS-R1a signaling converge on the somatotroph through different second messengers (cAMP and calcium/IP3 respectively) and are reported to be synergistic. A pre-combined format exists for that purpose in the CJC-1295 no DAC + ipamorelin blend.

With DAC

The albumin-bound form provides continuous GHRH-receptor stimulation. A published analysis of growth hormone secretion patterns found that pulsatility was preserved under sustained exposure, with the main change being a rise in basal (trough) growth hormone levels and a corresponding increase in IGF-1. In a mouse model lacking endogenous GHRH, once-daily administration of CJC-1295 was reported to normalize body growth, while less frequent schedules produced partial effects. These findings make the DAC form a tool for studying how the somatotropic axis responds to tonic, as opposed to episodic, GHRH input.

Laboratory handling differences

Most of the handling guidance is common to both forms, with one important exception.

• Reconstitution: add diluent slowly down the wall of the vial and swirl gently until the cake dissolves. The step-by-step technique is described in how to mix peptides with bacteriostatic water.
• Concentration math: a 5 mg vial of CJC-1295 no DAC reconstituted with 2 mL gives 2.5 mg/mL, or about 0.74 mM at 3,368 g/mol. A 10 mg vial with the same volume gives 5 mg/mL. Figures can be checked with the calculator.
• Storage: lyophilized vials at −20 °C for the long term; reconstituted solutions at 2–8 °C, protected from light. More detail is in storing research peptides.
• Maleimide stability (DAC form only): the maleimide ring slowly hydrolyzes in water, faster at neutral-to-alkaline pH, to a ring-opened form that no longer reacts with thiols. A DAC peptide that has sat in solution may therefore lose its albumin-conjugating ability even though the peptide backbone is intact. For that reason the DAC form is best reconstituted close to the time of use, and buffers containing free thiols (DTT, β-mercaptoethanol, cysteine) should be avoided because they will consume the maleimide.
• In vitro caveat: in a cell-culture system, the DAC form only behaves as a long-lived conjugate if albumin with a free Cys34 is present. In protein-free buffer the two forms act as similar GHRH-receptor agonists.

Analytical identification

Because two different molecules share a name, the certificate of analysis is the reliable way to know which one is in a vial. The mass spectrometry result is the distinguishing figure: approximately 3,368 Da for the no-DAC peptide and approximately 3,647 Da for the DAC form, a difference of about 279 Da that corresponds to the added lysine and maleimidopropionyl group. HPLC retention also differs because the DAC group adds hydrophobic character. Batch documents are available on the COA page.

Which form fits which experiment?

• Acute signaling and pulse studies: the no-DAC peptide suits experiments that examine a single GHRH-receptor stimulus, cAMP accumulation time courses, or synergy with ghrelin mimetics such as ipamorelin.
• Chronic exposure models: the DAC form suits designs that ask how sustained GHRH-receptor activation affects basal growth hormone output, IGF-1 production or somatotroph adaptation.
• Reference comparisons: unmodified GHRH(1-29), available as sermorelin, is a useful baseline for quantifying what the four substitutions contribute on their own.

The full catalog of GHRH analogs and secretagogues is listed in the shop.

Common points of confusion

• The names are used loosely. A label reading only "CJC-1295" does not say which molecule is inside. The presence or absence of DAC should be stated explicitly and confirmed by the reported mass.
• Persistence is not potency. The DAC group does not make the peptide a stronger agonist at the GHRH receptor; the pharmacophore is the same. It changes how long the ligand remains available.
• Equal masses are not equal moles. Because the DAC form is about 8% heavier, 1 mg contains roughly 0.27 µmol, against roughly 0.30 µmol for the no-DAC peptide. Side-by-side experiments should be matched on a molar basis.
• Neither form is a growth hormone analog. Both act upstream, at the pituitary GHRH receptor, and depend on functional somatotrophs to produce any downstream signal. In models lacking that receptor, neither is expected to be active.

Frequently asked questions

Is CJC-1295 without DAC the same as Mod GRF 1-29?

Yes. "CJC-1295 without DAC" and "Modified GRF (1-29)" refer to the same 29-residue peptide: GHRH(1-29) with D-Ala2, Gln8, Ala15 and Leu27 substitutions and no albumin-binding group. Strictly speaking, the name CJC-1295 originally referred only to the DAC-containing compound.

What does DAC stand for?

Drug Affinity Complex. It describes a reactive maleimide group attached through a lysine linker, which forms a covalent bond with the free thiol at cysteine 34 of serum albumin.

Why does the DAC form persist so much longer?

Once bonded to albumin, the peptide is too large to be filtered by the kidney, is shielded from proteases, and circulates for as long as its carrier protein. Published pharmacokinetic data put its half-life at roughly six to eight days, compared with about thirty minutes for the no-DAC peptide.

Can the two forms be told apart on a COA?

Yes. The observed mass is the clearest indicator: about 3,368 Da without DAC and about 3,647 Da with DAC. The molecular formula and HPLC retention time will also differ between the two.