CJC-1295 DAC vs no DAC: what 279 daltons change

What the linker is

Both molecules descend from the 1-29 fragment of human growth-hormone-releasing hormone, the shortest piece of the 44-residue hormone that keeps full activity [Rivier et al., 1982]. ConjuChem's chemists first made the fragment more durable by swapping four residues (D-alanine at 2, glutamine at 8, alanine at 15, leucine at 27), which closes the sites where dipeptidyl peptidase IV and other enzymes cut the native sequence.

Then they added a thirtieth residue, a lysine carrying an N-epsilon-3-maleimidopropionamide group. The maleimide is the working part: within minutes of a subcutaneous injection it reacts with the single free thiol on serum albumin, cysteine 34, and from then on the peptide travels as an albumin conjugate. In rats the conjugate was still detectable in plasma beyond 72 hours, and a Western blot of the plasma showed the peptide riding on the albumin band from 15 minutes onward [Jetté et al., 2005].

"DAC" is ConjuChem's trade name for that maleimide-lysine tail: Drug Affinity Complex. Remove the tail and what remains is the 29-residue tetrasubstituted analogue. The literature does not give the tail-less peptide a name of its own, because ConjuChem never developed it as a product; the forum name Mod GRF 1-29 filled the gap, and its history is told separately.

Half-life: minutes versus a week

The tail changes clearance by three orders of magnitude. In healthy adults, CJC-1295 with DAC had an estimated half-life of 5.8 to 8.1 days, and a single injection kept mean GH 2 to 10-fold above baseline for 6 days or more and IGF-1 1.5 to 3-fold above baseline for 9 to 11 days [Teichman et al., 2006]. Ionescu and Frohman, working from the same data, simply call it an 8-day half-life [Ionescu et al., 2006].

For the linker-free peptide there is no human number, because nobody has published a pharmacokinetic study of it. The nearest published relatives are the parent GHRH(1-29) sequence, which Corpas and colleagues injected subcutaneously twice a day to sustain its effect in men aged 68 [Corpas et al., 1992], and the rat comparison in the ConjuChem paper, where the GH effect of unmodified hGRF(1-29) was measured over two hours while the DAC conjugate persisted beyond three days [Jetté et al., 2005]. The four substitutions slow enzymatic breakdown, but they do not stop renal clearance of a 3.4 kDa peptide; the honest description is "minutes, not measured".

Pulse versus plateau

The objection to a week-long GHRH signal was physiological: GH is secreted in pulses, mostly during sleep, and a continuous stimulus might flatten the pattern that tissues seem to need. Ionescu and Frohman tested exactly that. Healthy men aged 20 to 40 had blood drawn every 20 minutes for 12 hours overnight, then received one injection of 60 or 90 µg/kg, and repeated the night of sampling a week later.

The pulses came back with the same frequency and the same amplitude. What the injection had changed was the floor: trough GH was 7.5 times higher (P < 0.0001), and that raised floor accounted for a 46 % rise in mean GH and a 45 % rise in IGF-1. The two doses were indistinguishable [Ionescu et al., 2006].

The no-DAC form does the opposite thing by construction. Each injection is a single stimulus that the pituitary answers with one pulse and then clears. That is the shape a GHRP produces as well: ipamorelin infused over 15 minutes gave one GH episode peaking at 0.67 hours and then an exponential decline to negligible levels, at every dose tested [Gobburu et al., 1999]. Put the two shapes side by side and the design logic of the research-market blend becomes visible: two short-acting peptides, two receptors, one pulse per injection. The mechanism is expanded in what is CJC-1295 ipamorelin.

Injection frequency in the studies

Frequency follows from half-life, and the published schedules say so plainly. The DAC form was given once, then once a week or once every two weeks, and IGF-1 stayed above baseline for up to 28 days after the last dose [Teichman et al., 2006]. In GHRH-knockout mice, which clear the conjugate faster than humans, 2 µg every 24 hours normalised body length and weight over 5 weeks, while every 48 or 72 hours did not fully [Alba et al., 2006].

The parent GHRH(1-29) sequence, the best available stand-in for the no-DAC form, needed two injections a day for 14 days to lift 24-hour GH and IGF-1 in old men to the values of men in their twenties, and only at the 1 mg dose, not at 0.5 mg [Corpas et al., 1992].

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Which one belongs in a blend

A "CJC-1295 ipamorelin" vial pairs a GHRH-receptor agonist with a ghrelin-receptor agonist so that both act on the same pulse. Ipamorelin is gone in a few hours; a GHRH analogue that persists for a week is not acting on the same pulse, it is acting on all of them. That is why the blend that circulates in the research market uses the no-DAC form, and why a listing that claims to combine the DAC form with ipamorelin describes a product whose two halves work on different time scales. The for-sale guide treats that as one of the nine things to check before reading further.

Telling them apart on a certificate

The label cannot settle which form is in a vial; the mass can. Lysine plus the maleimidopropionyl group adds 279.4 daltons, so a deconvoluted mass near 3,647 is the DAC form and one near 3,368 is the no-DAC form, whatever the label says. That arithmetic needs nothing beyond the sequence published in 2005 [Jetté et al., 2005]. The supplier page this site links to prints both component masses on each lot certificate, which is the reason it is the one link.

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