DAC (Drug Affinity Complex) is a maleimidoproprionic acid group attached to the C-terminal end of a peptide. Once in circulation it reacts with the free cysteine-34 thiol of serum albumin, forming a covalent thioether bond that turns the small peptide into a passenger on a 66 kDa carrier protein. Albumin is recycled through the neonatal Fc receptor rather than filtered by the kidney, so the bound peptide inherits albumin’s long residence time.
Why DAC matters in peptide research
The canonical example is CJC-1295 with DAC, a tetrasubstituted GHRH (1-29) analog. Published pharmacokinetic work in humans reported a terminal half-life measured in days for the DAC construct, against minutes for unmodified GHRH fragments such as CJC-1295 without DAC. For a study design that difference is structural, not cosmetic: DAC material produces a sustained elevation of the signal being measured, while non-DAC material produces discrete pulses. Rodent and human studies of the two constructs are therefore not interchangeable, and results reported for one should not be read onto the other.
DAC also changes handling assumptions. Because the modification survives lyophilisation but relies on an intact maleimide, hydrolysed or heat-stressed material can lose the albumin-binding function while still reading as the parent peptide on a mass check. Compare the CJC-1295 with DAC overview against the general stability and half-life guide.