CJC-1295 No DAC

This compound is a 29-residue analog of the growth hormone releasing hormone N-terminal fragment, carrying four substitutions and a C-terminal amide. It is widely referred to as modified GRF(1-29). Each substitution addresses a distinct and identifiable liability in the native sequence, which makes it an unusually legible piece of peptide engineering.

D-alanine at position 2 blocks dipeptidyl peptidase-4 cleavage, the fastest degradation route for the native fragment. Glutamine replaces asparagine at position 8, eliminating the deamidation and succinimide rearrangement that limits the shelf life of the unmodified sequence. Alanine at position 15 is reported to increase potency. Leucine replaces methionine at position 27, removing the residue most prone to oxidation. It engages the GHRH receptor, a class B G-protein-coupled receptor distinct from the ghrelin receptor targeted by ipamorelin.

The comparative literature between this analog and unmodified sermorelin is the most informative body of work for understanding it, because the two differ only in those four positions and the resulting difference in persistence is attributable to identifiable chemistry rather than to unresolved pharmacology.

In-vitro characterisation uses cAMP accumulation assays in cells expressing the GHRH receptor, with pituitary cell preparations as the ex-vivo system for examining releasing activity directly. Stability studies comparing the analog against the native fragment in serum and in buffer are a substantial part of the reported work, since resistance to degradation rather than altered receptor affinity is the design objective.

Reversed-phase HPLC establishes purity and mass spectrometry confirms identity, reported per lot on the Certificate of Analysis. The D-alanine at position 2 introduces the same diastereomer risk found in any D-configured sequence: epimerisation to L-alanine yields an identical mass, returns the sequence to dipeptidyl peptidase-4 susceptibility, and is detectable only by chromatography.

C-terminal amidation requires separate confirmation, since the free-acid form differs by one dalton and is reported as considerably less active at the receptor. At 29 residues the synthesis is long enough that deletion sequences are the dominant impurity class, and the four substitutions must each be confirmed present, since a lot reverting to a native residue at any of those positions carries the corresponding degradation liability back with it.