CJC-1295 with DAC, explained: four swaps and a chemical hook

CJC-1295 is the clearest worked example of peptide engineering in this catalogue, because you can point at each modification and say exactly what problem it solves.

The starting material

GHRH is 44 amino acids long. Only the first 29 are needed to activate the receptor; the rest can be removed without losing activity. That fragment, GHRH(1-29), is the basis for several compounds and is a licensed medicine in its own right in some markets under the name sermorelin.

The trouble is that GHRH(1-29) is fragile. It is cleaved at the N-terminus by DPP-4 within minutes, and it also degrades chemically at an asparagine residue. A supplied fragment is gone almost immediately.

What the four substitutions do

CJC-1295 carries four changes to that 29-residue sequence:

1. D-Ala at position 2. Swapping in the D-isomer of alanine at the DPP-4 cleavage site. The enzyme recognises the natural L-form; the mirror image does not fit. Tesamorelin solves the same problem differently, with an acyl cap.
2. Gln at position 8. Replaces an asparagine that is prone to deamidation, a slow chemical change that alters the molecule on the shelf and in solution.
3. Ala at position 15. A substitution reported to improve potency at the receptor.
4. Leu at position 27. Replaces a methionine, which is vulnerable to oxidation.

Two of the four defend against enzymes, two against ordinary chemistry. None of them extends the half-life past an hour or so on their own.

What DAC actually is

DAC stands for Drug Affinity Complex, and it is the part that changes the compound's character completely.

A maleimidopropionyl group is attached to the peptide at the lysine at position 30. Maleimide chemistry is specific: it reacts with free thiol groups. Serum albumin carries a free cysteine at position 34, and that cysteine has a free thiol. When the peptide meets albumin in the bloodstream, the maleimide and the thiol form a covalent bond.

The distinction from the albumin binding used in the incretin compounds is worth being precise about. Tirzepatide uses a fatty acid chain that binds albumin reversibly, by physical association. DAC forms an actual chemical bond. The peptide is not riding on albumin; it is attached to it. The reported half-life is measured in days rather than minutes.

Remove the DAC linker and you have a different compound, often sold as modified GRF(1-29) or CJC-1295 no-DAC, with a half-life around thirty minutes. The two versions compared properly.

What has been studied

Jetté and colleagues described the albumin bioconjugate chemistry and receptor activation in rats in Endocrinology in 2005. Teichman and colleagues reported a study in healthy adults in the Journal of Clinical Endocrinology and Metabolism in 2006, measuring prolonged stimulation of growth hormone and IGF-1 secretion.

That is a small literature by the standards of the incretin compounds, and it is most of what exists.

Regulatory status

CJC-1295 has no marketing authorisation as a medicine anywhere. In the UK it may lawfully be bought, sold and held for laboratory research, and may not be sold or advertised for human or veterinary use.

It is on the WADA Prohibited List under growth hormone secretagogues, prohibited at all times rather than in competition only. What being on the list does and does not mean.

What matters for research supply

The DAC and no-DAC versions look almost identical on a label and are not the same compound. That makes identity the first check rather than the third.

1. Identity, and specifically which version. The DAC linker adds mass. A certificate should make clear which molecule was analysed. How to read one.
2. Purity, with the method named. What HPLC and mass spectrometry each establish.
3. Quantity, stated separately. Purity is not quantity.
4. Batch traceability — certificate, carton and batch lookup agreeing.
5. Storage — 2 to 8°C, dark, not frozen.

How Biovanta supplies it

CJC-1295 DAC 10 mg is supplied in a factory-sealed pre-filled pen with sterile needles and prep swabs, manufactured in Switzerland and dispatched from the UK. Every batch carries an independent Janoshik report with a verification key that opens on the laboratory's own site; the testing page shows which batches have one. Supplied strictly for in-vitro laboratory research.