Conjugation to albumin-binding molecule tags as a strategy to improve both efficacy and pharmacokinetic properties of the complement inhibitor compstatin.

ABSTRACT: The compstatin family of complement inhibitors has shown promise in various immuno-inflammatory disorders. Although recent analogues show beneficial pharmacokinetics, further extension of the plasma half-life is expected to benefit systemic application of these peptidic inhibitors. We therefore synthesized conjugates of compstatin analogues and albumin-binding molecules (ABM) to increase circulatory residence. Equilibrium dialysis in complement-depleted serum showed a marked increase in plasma protein binding from <8 % to >99 % for a resulting chimera (ABM2-Cp20). Further analysis confirmed interaction with albumin from different species, primarily via site II. Importantly, ABM2-Cp20 bound 20-fold stronger to its target protein C3b (KD =150 pM) than the parent peptide. Kinetic and in silic

SUBMITTER: Huang Y 

PROVIDER: S-EPMC4177305 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature