Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides

• DOI: 10.1038/ncomms16092
• Publication Date: 2017-07-17T09:25:59Z
• Authors: Alessandro Zorzi; Simon J. Middendorp; Jonas Wilbs; Kaycie Deyle; Christian Heinis
• Keywords: Human serum albumin; Serum Albumin

The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment a broad range diseases that require prolonged drug half-lives. An intriguing approach extending peptide circulation times works through 'piggy-back' strategy which bind via ligand to long-lived serum protein albumin. In accordance with strategy, we developed an easily synthesized albumin-binding based on peptide-fatty acid chimera has high affinity human albumin (Kd=39 nM). This prolongs elimination half-life cyclic rats 25-fold over seven hours. Conjugation factor XII inhibitor anti-thrombotic therapy extends from 13 minutes five hours, inhibiting coagulation eight hours rabbits. high-affinity could potentially extend several days, substantially broadening application as therapeutics.