CJC-1295 Without DAC (Mod GRF 1-29): The Four Substitutions Explained

"CJC-1295 without DAC," sold under the shorthand Mod GRF 1-29, is a 29-residue peptide built on the active front end of human growth hormone-releasing factor (GRF, also called GHRH). It carries four amino acid swaps, and each one has a history in the literature. This Vial Post explainer walks through the sequence change by change, shows where the "DAC" version branches off, and lists the numbers an analytical lab would check.

Nothing here is guidance on use in people or animals. The Vial Post covers this peptide only as a subject of laboratory and literature research.

Where the 29 Residues Come From

• The parent hormone. In 1982 Guillemin and colleagues isolated a 44-amino-acid peptide with growth hormone-releasing activity from a human pancreatic tumor and reported its full sequence; the synthetic copy was fully active in vitro and in vivo (Guillemin 1982).
• The shortened form. Ling and colleagues synthesized C-terminally shortened versions in 1984. Potency fell gradually down to hGRF(1-34), but hGRF(1-31)NH2, (1-30)NH2 and (1-29)NH2 all held at about 50% of the full hormone in rat pituitary cell cultures (Ling 1984).
• The reference peptide. hGRF(1-29)NH2 is the peptide known as sermorelin (Knoop 2016).

The Four Substitutions

Doping-control chemists at the German Sport University list CJC-1295 as (D-Ala2, Gln8, Ala15, Leu27)-GRF amide and give its one-letter sequence as Y-dA-DAIFTQSYRKVLAQLSARKLLQDILSR-NH2 (Knoop 2016). Set against the native sequence published in 1982 (Guillemin 1982), the changes are:

1. Position 2: Ala to D-Ala. The main plasma enzyme that inactivates GRF is dipeptidylpeptidase IV (DPP-IV), which clips off the first two residues at the 2-3 bond. Frohman's group showed in 1989 that a D-amino acid at position 1 or 2 prevented that cleavage, and that plasma degradation of GRF runs mainly through DPP-IV and, to a lesser extent, trypsin-like enzymes (Frohman 1989). For background on D-residues, see Dynamite Peptides' explainer on D- vs L-amino acids. 2. Position 8: Asn to Gln. 3. Position 15: Gly to Ala. In Upjohn's bovine GRF program, swapping Gly15 for Ala15 was only marginally effective at improving in vitro bioactivity on its own. It was combined with position-2 changes in a series of analogs, and the team compared them against an earlier super-potent analog, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)NH2 (Kubiak 1993). 4. Position 27: Met to Leu. The Upjohn analogs were built on a Leu27 backbone (Kubiak 1993).

Knoop and colleagues also list a one-change relative, CJC-1293, which is sermorelin with only the D-Ala2 swap (Knoop 2016).

Where "DAC" Branches Off

The 2005 ConjuChem paper that named CJC-1295 describes the tetrasubstituted hGRF(1-29) plus an extra C-terminal lysine carrying a maleimidopropionamide group (Jetté 2005). That reactive group bonds to the free thiol on Cys34 of serum albumin. Key findings in rats (Jetté 2005):

• the albumin conjugates were more stable against DPP-IV in vitro and stayed active in a pituitary cell assay;
• CJC-1295 gave a 4-fold larger growth hormone area under the curve over 2 hours than hGRF(1-29);
• the compound was still present in plasma beyond 72 hours, and an immunoreactive band at the albumin position appeared within 15 minutes.

A 2006 clinical pharmacology study of that albumin-binding form estimated its half-life at 5.8 to 8.1 days (Teichman 2006). The "no DAC" peptide lacks the lysine-maleimide add-on, so those long-half-life figures describe the other molecule. Dynamite Peptides covers that version in its explainer on how CJC-1295 with DAC differs.

What the Doping Labs Measured

Knoop and colleagues built an immunoaffinity and high-resolution mass spectrometry test for four GRF-type peptides (Knoop 2016):

• Masses: monoisotopic 3365.9 Da for CJC-1295, against 3355.8 Da for both sermorelin and CJC-1293, seen at m/z 674 (z = 5) and m/z 672 (z = 5).
• Same mass, different handedness: sermorelin and CJC-1293 differ only by L-Ala versus D-Ala at position 2 and were not separated chromatographically under the study's conditions.
• Detection limit: below 50 pg/mL in human plasma for each target.
• Stability in rats: after intravenous administration, CJC-1295, CJC-1293 and tesamorelin were still detected in plasma at 4 and 8 hours, the last time point. Sermorelin and CJC-1293 were readily broken down compared with CJC-1295, but no truncated metabolites turned up, which the authors read as rapid, unspecific degradation. The authors note that their results were qualitative only.

An earlier report came from Norway. In 2009, at the request of police and customs authorities, the Norwegian Doping Control Laboratory analyzed an unknown pharmaceutical preparation and found a 29-amino-acid peptide with a C-terminal amide whose sequence matched the product sold as CJC-1295 (Henninge 2010). It is listed as a prohibited substance under section S2 of the WADA list (Henninge 2010).

Frequently Asked Questions

Is "Mod GRF 1-29" a different compound from CJC-1295 without DAC? Vendors use both labels for the same design: the tetrasubstituted GRF(1-29) amide without the albumin-binding lysine. The published sequence is (D-Ala2, Gln8, Ala15, Leu27)-GRF amide (Knoop 2016).

Why does position 2 matter so much? DPP-IV inactivates GRF by cutting the 2-3 bond, and a D-residue at position 1 or 2 blocks that cut (Frohman 1989).

What mass should a COA show? The monoisotopic mass reported for the peptide is 3365.9 Da (Knoop 2016). A result near 3355.8 Da would point to sermorelin or CJC-1293 instead. See our explainer on HPLC versus mass spec and our companion piece on tesamorelin.

For research and educational use only. This article is not medical advice and does not describe dosing or human use.