Glossary
DAC (Drug Affinity Complex)
DAC is a maleimide linker that couples a peptide to serum albumin, stretching its half-life from minutes to days. What that changes in research design.
DAC, the Drug Affinity Complex, is a maleimidoproprionic acid group fixed to the C-terminal end of a peptide. After entering the circulation it reacts with the free thiol of cysteine-34 on serum albumin, creating a covalent thioether bond that makes the small peptide ride along on a 66 kDa carrier protein. Instead of being filtered out by the kidney, albumin is recycled via the neonatal Fc receptor, so the attached peptide takes on albumin’s long residence time.
Implications for study design
The standard example is CJC-1295 with DAC, a GHRH (1-29) analog carrying four substitutions. Published human pharmacokinetic data gave the DAC construct a terminal half-life counted in days, compared with minutes for unmodified GHRH fragments such as CJC-1295 without DAC. For an experimental design this is a fundamental difference, not a detail: material with DAC yields a prolonged rise in the measured signal, whereas material without it yields separate pulses. Rodent and human data for the two constructs are therefore not interchangeable, and findings for one must not be transferred to the other.
DAC alters handling assumptions as well. The modification withstands lyophilisation but depends on the maleimide staying intact, so hydrolysed or heat-damaged material may lose albumin binding while a mass check still identifies it as the parent peptide. Set the CJC-1295 with DAC overview against the general stability and half-life guide.
Related terms
PEGylation · stability · GHRH analogs collection