CJC-1295 With and Without DAC: What the Modification Changes

CJC-1295 is sold and studied in two forms that are frequently conflated. The difference is a single chemical addition, but it changes the compound’s pharmacokinetic profile enough that the two should be treated as separate research materials.

The parent sequence

Both forms are built on a modified fragment of growth hormone-releasing hormone — specifically GHRH(1-29), the shortest fragment that retains full receptor activity. Native GHRH(1-29) is degraded rapidly, with dipeptidyl peptidase-4 cleaving between residues 2 and 3. CJC-1295 carries four amino acid substitutions that resist that cleavage and reduce other degradation routes.

What DAC adds

DAC stands for Drug Affinity Complex: a maleimidoproprionic acid group attached at the C-terminus. That group reacts with a free cysteine thiol on circulating serum albumin, forming a covalent conjugate. The peptide is then carried by albumin, a protein with a multi-day circulating half-life, rather than clearing on its own timescale.

The practical consequence is a large difference in duration of exposure between the two forms. Without DAC, the modified GHRH fragment retains the substitutions that resist enzymatic degradation but has no albumin-binding anchor, so exposure is comparatively brief. This is why the no-DAC form is sometimes referred to in the literature and in supplier catalogues as modified GRF(1-29).

Why the distinction matters experimentally

GHRH receptor signalling is pulsatile in vivo. A short-exposure agonist and a long-exposure agonist therefore probe different questions: one approximates a pulse, the other produces sustained receptor occupancy. Studies comparing pulsatile versus continuous GHRH-receptor stimulation are not interchangeable, and an experimental design written for one form does not transfer to the other.

The published pharmacology of CJC-1295 and of albumin-binding peptide conjugates generally is indexed at PubMed, and the broader albumin-conjugation approach at this search.

Combination with a secretagogue

CJC-1295 is often studied alongside a growth hormone secretagogue receptor agonist such as ipamorelin. The two act on different receptors — GHRHR and GHSR-1a respectively — which is the stated rationale for examining them together in the same model. We stock the no-DAC form and a CJC-1295 and ipamorelin blend, alongside other growth hormone pathway peptides.

Labelling caution

Because both forms share the name CJC-1295, catalogue listings that omit “DAC” or “no DAC” are ambiguous. Confirm which form a certificate of analysis describes before using it to plan an experiment — the molecular weights differ, and a mass spectrometry trace is the clearest way to tell them apart.

ExoLabz supplies compounds for laboratory research use only. Nothing on this page is medical advice or a suggestion of human or veterinary use. Certificates of analysis for each compound are published on this site.

The two forms, side by side

The numbers are the fastest way to tell them apart, and they are the numbers to look for on a certificate:

• Without DAC (also sold as Mod GRF 1-29): C152H252N44O42, about 3,367.9 g/mol, CAS 863288-34-0. Sequence [D-Ala2, Gln8, Ala15, Leu27]-GRF(1-29) amide.
• With DAC: C165H269N47O46, about 3,647.2 g/mol, CAS 446262-90-4.

The difference is roughly 280 Da. That is a large, unambiguous gap for a mass spectrometer, which is why the observed mass on the certificate is the only check worth relying on here. Two vials labelled “CJC-1295” can contain molecules 280 Da apart, and no amount of purity reporting will tell you which one you have if the mass is not stated.

The four substitutions, and what each one is for

Before the DAC question arises, the base molecule is already a modified sequence rather than the native fragment. GRF(1-29) is the first 29 residues of the 44-residue native hormone; the modified version carries four deliberate substitutions, and each targets a specific degradation route:

• D-Ala at position 2 — the native alanine at position 2 is the dipeptidyl peptidase-4 cleavage site. Substituting the D-enantiomer removes the recognition geometry that enzyme needs. This single change accounts for most of the resistance to rapid degradation.
• Gln at position 8 — replaces an asparagine, removing an asparagine-glycine style deamidation liability at that position.
• Ala at position 15 — replaces a glycine, altering local flexibility.
• Leu at position 27 — replaces a methionine, which removes the sequence’s oxidation-capable residue. This is why the no-DAC form does not carry the “mass 16 above target” oxidation impurity that a methionine-containing sequence would.

Read as a set, these are four separate answers to four separate ways a peptide can be lost. Our note on what sets a peptide’s half-life covers the general pattern.

What the DAC addition actually is

The drug affinity complex is a maleimidoproprionic acid group attached to the peptide. Its function is not receptor-related at all: it provides a reactive handle that forms a covalent bond with a nucleophilic thiol on circulating albumin. The peptide is then carried bound to a large, long-lived protein rather than circulating free.

So the two forms differ in persistence, not in what they bind. Both act at the GHRH receptor; the modification changes how long the molecule remains available. That distinction is what makes them different research tools rather than different doses of the same tool: a fixed-incubation assay reads them differently, and any comparison that does not state the incubation is not comparing like with like. See Ki, IC50 and EC50.

Analytical consequences of the difference

The maleimide handle is reactive by design, and that has practical implications the no-DAC form does not have:

• A reactive group can react with things other than albumin, including nucleophiles in a buffer or a stopper. It is the more condition-sensitive of the two forms.
• Hydrolysis of the maleimide gives a species that has lost its function while remaining nearly the same mass — a hard impurity to see.
• The added group is hydrophobic, so retention on a reverse-phase column shifts noticeably. A chromatogram of one form is not a reference for the other.

See where peptide impurities come from and how HPLC and mass spectrometry verify purity.

Why the two are confused so persistently

Three reasons, and knowing them is most of the defence. The name “CJC-1295” is used in the literature and in the market for both forms, sometimes without qualification. The no-DAC form has a second name, Mod GRF (1-29), which is often treated as a different compound rather than a synonym. And a 280 Da difference on a molecule of about 3,400 Da is under 10% — invisible to anything except a mass measurement.

The practical rule: treat the name as insufficient, and read the mass. A certificate that reports a purity percentage without an observed mass has not told you which molecule is in the vial.

Combined with a secretagogue

CJC-1295 is frequently studied alongside a growth hormone secretagogue-receptor agonist such as ipamorelin, and that is a two-receptor experiment rather than a stronger single-receptor one: GHRH analogs act at the GHRH receptor, secretagogues at GHSR-1a, and the two receptors couple differently. See GHRH analogs versus growth hormone secretagogues and Ipamorelin and GHSR-1a selectivity. Where the two are supplied pre-combined, the per-component mass is what makes the vial interpretable — see what cost per milligram hides.