Peptide Research

CJC-1295 without DAC, also known as Modified GRF(1-29), is a synthetic analogue of the first 29 amino acids of growth hormone-releasing hormone (GHRH) with four amino acid substitutions designed to improve metabolic stability. The modifications (Ala at position 2 to D-Ala, Asn at position 8 to Gln, Ala at position 15 to Ala (retained), and Met at position 27 to Leu) confer resistance to DPP-4 and other proteolytic enzymes while preserving full GHRH receptor binding affinity.

The 'without DAC' designation distinguishes it from CJC-1295 with DAC (Drug Affinity Complex), which includes a maleimidopropionic acid linker that enables covalent binding to serum albumin. Without the DAC modification, this version has a shorter half-life of approximately 30 minutes, producing a more physiological acute GH pulse rather than the sustained GH elevation seen with the DAC version.

CJC-1295 without DAC binds GHRH receptors on pituitary somatotrophs and activates the Gs-cAMP-PKA pathway to stimulate GH release. Its shorter-acting nature produces GH pulses that more closely mimic natural secretion patterns, which some researchers prefer for maintaining physiological feedback regulation. It is frequently studied in combination with ghrelin receptor agonists like ipamorelin for synergistic GH release.

CJC-1295 with DAC is the albumin-conjugating version of CJC-1295, featuring a Drug Affinity Complex (DAC) — a reactive maleimidopropionic acid group that forms a covalent bond with serum albumin after subcutaneous injection. This albumin conjugation dramatically extends the circulating half-life from approximately 30 minutes (without DAC) to 6-8 days, enabling sustained elevation of GH and IGF-1 from a single administration.

Once bound to albumin, the CJC-1295-DAC conjugate circulates with the albumin protein, slowly releasing active peptide that continuously stimulates GHRH receptors on pituitary somatotrophs. This produces a pattern of sustained GH elevation rather than the acute pulsatile pattern seen with the non-DAC version. Teichman et al. demonstrated in a landmark clinical study that a single injection produced dose-dependent GH increases sustained for up to 6 days and IGF-1 elevation for 9-11 days.

The sustained-release pharmacokinetics of CJC-1295 DAC are advantageous for research protocols requiring consistent GH/IGF-1 elevation, but some researchers prefer the non-DAC version because it better preserves the natural pulsatile GH secretion pattern. The choice between versions depends on the specific research question being addressed.