title: Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance.
abstract: BACKGROUND
  Human C1-esterase inhibitor (C1-INH) is a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key down-regulator of the complement and contact cascades. The potentiation of C1-INH by heparin and other glycosaminoglycans (GAGs) regulates a broad spectrum of C1-INH activities in vivo both in normal and disease states. SCOPE OF RESEARCH: We have studied the potentiation of human C1-INH by heparin using Surface Plasmon Resonance (SPR), circular dichroism (CD) and a functional assay. To advance a SPR for multiple-unit interaction studies of C1-INH we have developed a novel (consecutive double capture) approach exploring different immobilization and layout.
  
  
  CONCLUSIONS
  Our SPR experiments conducted in three different design versions showed marked acceleration in C1-INH interactions with complement protease C1s as a result of potentiation of C1-INH by heparin (from 5- to 11-fold increase of the association rate). Far-UV CD studies suggested that heparin binding did not alter C1-INH secondary structure. Functional assay using chromogenic substrate confirmed that heparin does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation.
  
  
  CONCLUSIONS
  This is the first report that directly demonstrates a significant acceleration of the C1-INH interactions with C1s due to heparin by using a consecutive double capture SPR approach. The results of this study may be useful for further C-INH therapeutic development, ultimately for the enhancement of current C1-INH replacement therapies.
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors: Mohsen
authors: M
authors: Rajabi
authors: Evi
authors: E
authors: Struble
authors: Zhaohua
authors: Z
authors: Zhou
authors: Elena
authors: E
authors: Karnaukhova
mesh_terms: D050718:Complement C1 Inhibitor Protein / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D050718:Complement C1 Inhibitor Protein; D006493:Heparin