Drug Affinity Complex (DAC)

A Drug Affinity Complex, or DAC, is a reactive group that attaches a peptide to serum albumin. The group is 3-maleimidopropionic acid on the epsilon-amine of a C-terminal lysine; albumin's one free thiol, cysteine 34, reacts with the maleimide to form a stable thioether, so within minutes of injection the peptide is covalently attached to albumin and shares its three-week half-life. In a sequence block it is a parenthetical on the final K.

The compound built on it is CJC-1295, a GHRH(1-29) amide with four stabilising substitutions (D-Ala2, Gln8, Ala15, Leu27) plus a thirtieth residue, the lysine bearing the maleimide. In healthy adults a single injection raised growth hormone and IGF-1 for a week or more, with an estimated half-life of six to eight days against about thirty minutes without the linker. Development stopped in the mid-2000s; it was never approved.

The design contrast is with lipidation, which binds albumin reversibly. Semaglutide's fatty acid docks and lets go, so a free fraction is always present; a DAC peptide is permanently tethered, which turns the exposure pattern from pulses into a continuous low level. For a releasing hormone the pituitary normally sees in pulses that is a different pharmacology, not a longer version of the same one.

The bite is in the naming. The peptide without the linker is modified GRF(1-29), also sold as CJC-1295 without DAC, a pharmacologically different compound sharing twenty-nine residues; the extra lysine and linker add close to 280 daltons, so a molecular weight near 3,370 is the linkerless peptide and one near 3,650 carries the DAC. The maleimide also hydrolyses in solution to an unreactive open ring, so a reconstituted DAC peptide can lose the group it depends on.