Standard peptides degrade within minutes to hours in plasma. The propiolamide warhead is an N-propargylacrylamide derivative — a Michael acceptor with moderated electron-withdrawing character. When it encounters a nucleophilic thiol (cysteine) or amine (lysine) on the target receptor, it undergoes Michael addition, forming a covalent adduct.
Crucially: this bond is reversible. The adduct hydrolyzes over 2–4 weeks, releasing the drug without permanent receptor damage. Think Velcro, not superglue. The receptor itself becomes the depot — no albumin binding, no large injection volumes, no albumin interference.
Reversible Covalence
Michael addition to Cys / Lys residues. Bond hydrolyzes with t½ of 2–4 weeks. No permanent adduct, no receptor damage.
Extended Duration
Receptor occupancy maintained for 14–28 days per dose. Single injection replaces daily or weekly regimens.
Clean Safety Profile
Does not cross the BBB when attached to large peptides (>800 Da). Does not alkylate DNA. No permanent off-target adducts.