CJC-1295 with DAC vs without DAC: what the drug affinity complex changes

At a glance

Two materials circulate under the same CJC-1295 name, and the abbreviation DAC is the only thing distinguishing them on most labels. DAC stands for drug affinity complex, and it is a chemical addition to the peptide rather than a formulation choice or a purity grade. Everything else about the two forms, including the core sequence, is shared. All compounds discussed are supplied strictly as laboratory research materials. They are not for human or veterinary use, and nothing here is medical advice.

• Shared core. Both forms are built on a tetrasubstituted growth hormone releasing hormone (1-29) amide, the shortened analogue family generally written as GHRH(1-29) or GRF(1-29)-amide.
• The difference. The DAC form carries an added maleimidopropionic acid lysine linker. The form without DAC does not.
• What the linker does chemically. The maleimide group is a thiol-reactive handle, and the published characterisation describes conjugation to serum albumin through that handle.
• Alternative names. The form without DAC is frequently catalogued as modified GRF (1-29), which describes the same substituted 29-residue amide.
• Research model weighting. The DAC form has a named rat pituitary receptor study behind it. The unmodified substituted analogues have a longer pharmacokinetic literature, part of which is clinical and therefore outside the scope of a catalogue like this one.
• How each is supplied. Both as lyophilised powder in a sealed vial with a lot-specific certificate of analysis.

What CJC-1295 without DAC is

The form without DAC is a 29-residue amide corresponding to the biologically active N-terminal fragment of growth hormone releasing hormone, carrying four amino acid substitutions relative to the native sequence. The substitutions are the point of the molecule. Native GHRH(1-29) is a poor bench reagent because it is cleaved rapidly in serum, and the substituted analogue family was designed around that problem. One of the four, the D-alanine at the second position, is named directly in the pharmacokinetic literature (PMID 7962295), where its incorporation into the (1-29) amide was the variable under study.

The peptide has no DAC linker, no maleimide, and no albumin-binding handle. Its identity on a mass spectrum is simply the substituted 29-residue amide, and a certificate for this material should show a single dominant species at that mass with no linker adduct present. The absence of the linker is a verifiable analytical fact rather than a labelling claim, which is one reason mass data belongs on every certificate; the reading method is set out in mass spectrometry peptide testing.

The published record for the unmodified substituted analogues is largely pharmacokinetic. A 1988 evaluation catalogues substituted GRF(1-29)-amide analogues and compares their measured clearance and stability parameters against the parent sequence (PMID 2896343). The 1994 report examining D-Ala2 incorporation is clinical: clinical literature exists for substituted GHRH(1-29) amide analogues in growth hormone axis pharmacokinetics, and it is outside the scope of a research-materials catalogue (PMID 7962295). Neither paper is cited here for an outcome. They are cited because they define what the substitutions were for and how the resulting molecules were measured.

What CJC-1295 with DAC is

The DAC form takes the same substituted GHRH(1-29) amide and appends a maleimidopropionic acid lysine linker. Maleimide chemistry is standard bioconjugation chemistry: the maleimide ring adds across a free thiol to form a stable thioether bond. Serum albumin carries an accessible free cysteine, which is what the linker was selected to reach. The resulting molecule is therefore not simply a peptide with a longer tail. It is a peptide designed to become a covalent albumin conjugate once it encounters serum.

The primary characterisation is a rat study. In rats, hGRF(1-29) albumin bioconjugates were assessed for activation of the GRF receptor on the anterior pituitary, with the work identifying CJC-1295 as the long-lasting analogue in the series (PMID 15817669). The measured variables in that model family are receptor activation at the pituitary and the persistence of the circulating conjugate, both read in the animal rather than inferred. Every mechanistic statement in the preceding sentences describes that rat model and nothing beyond it.

The analytical consequence for a bench user is that the two forms are not distinguished by potency claims on a label but by mass. The DAC form must show the linker mass; the form without DAC must not. Any lot whose mass data is absent or ambiguous on that point has not established which of the two materials is in the vial, whatever the label says. The catalogue documents are filed at certificates, and the verification workflow is in how to verify a peptide certificate of analysis.

Where the research models differ

Animal receptor work versus analogue pharmacokinetics

The DAC form's central citation is an in vivo rat study built around a receptor readout at the anterior pituitary (PMID 15817669). The literature for the unmodified substituted analogues is built instead around measured clearance and half-life parameters in pharmacokinetic evaluations (PMID 2896343, PMID 7962295). These are different experimental questions. One asks whether a receptor is engaged in a live rodent; the other asks how long a molecule persists and how fast it is removed.

Conjugation as an experimental variable

A study using the DAC form is, by construction, a study of a peptide-albumin conjugate as much as of the peptide. Any experiment run in a serum-free system removes the very partner the linker was designed for, which makes cell-culture work with the DAC form a different proposition from cell-culture work with the unmodified analogue. Investigators designing an in vitro comparison should decide in advance whether albumin is present in the medium, because that single choice changes what the DAC form is during the assay.

Timescale of measurement

The two forms are studied on different clocks. Receptor and pharmacokinetic work on a long-acting conjugate is sampled over extended windows in the rat model, while the shorter substituted analogue literature is sampled over much tighter ones. A protocol borrowed from one and applied to the other will sample at the wrong times, which is a design error rather than a compound property.

Choosing between them for a laboratory question

Neither form is a better molecule. They answer different questions, and the choice follows from the question on the protocol sheet.

• A question about receptor engagement at the pituitary in a rodent has a direct published precedent with the DAC form (PMID 15817669), including a defined species and tissue to compare against.
• A question about how substitution affects clearance and stability sits with the unmodified substituted analogue literature, where those parameters were the measured variables (PMID 2896343).
• A question about albumin conjugation chemistry itself, including linker efficiency, conjugate mass verification or thiol availability, requires the DAC form, since the form without DAC has no reactive handle at all.
• A short-window in vitro assay in serum-free medium is a poor fit for the DAC form for the structural reason given above, and the unmodified analogue is the cleaner reagent for that design.

The corresponding catalogue material is described in the CJC-1295 research guide and listed at the CJC-1295 product page, grouped with other cellular research materials.

Storage and handling

Both forms ship lyophilised and belong at minus 20 degrees Celsius or colder, sealed, dark and dry. Vials should reach room temperature before the stopper is broken, so that condensation does not settle onto the cake and start hydrolysis before the first aliquot is drawn.

The DAC form carries one handling consideration the unmodified peptide does not. Maleimide groups hydrolyse in aqueous solution, and the hydrolysed ring no longer reacts with thiols. That is a chemical property of maleimides generally rather than a measured shelf-life for this material, but it is the reason reconstituted DAC-linked peptide should not be held in solution as a convenience stock across many sessions. Aliquot once, label each tube with lot and date, and freeze.

Diluent selection is covered in the comparison of bacteriostatic water and sterile water, and the volume required for a target concentration should come from the reconstitution calculator rather than a mental estimate. Purity documentation for either form should be read against the standards described in HPLC peptide purity and what 99 percent peptide purity means.

All compounds discussed are supplied strictly as laboratory research materials. They are not for human or veterinary use, and nothing here is medical advice.

References

1. 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. 15817669
2. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. The Journal of clinical endocrinology and metabolism, 1994. 7962295
3. Pharmacokinetic evaluation of superactive analogues of growth hormone-releasing factor (1-29)-amide. Peptides, 1988. 2896343