Complement Function/Activity Test

Complement function or activity test allows for the determination of whether the protein is present and whether it has normal functional activity. A wide range of assays are now available in Creative Biolabs, such as Hemolysis assays (CH50 or AH50), Elisa Assays (c3a, c5a, FH, FB, C5b-9 or others), Complement Inhibitor Validation (IC50)......

Explore the collection of assays

Creative Biolabs is proud to offer compstain development services in a timely and cost-effective manner. With years of ample experiences in antibody drug development, our scientists are confident in providing a full range of compstain development services to promote the development of biopharmaceuticals. We offer turn-key or ala carte services customized to our client’s needs.


Therapeutic modulation of the human complement system is considered a promising approach for treating a number of pathological conditions. Owing to its central position in the cascade, component C3 is a particularly attractive target for complement-specific drugs. Compstatin, a cyclic tridecapeptide, which was originally discovered from phage-display libraries, is a highly potent and selective C3 inhibitor that demonstrated clinical potential in a series of experimental models. A combination of chemical, biophysical, and computational approaches allowed a remarkable optimization of its binding affinity towards C3 and its inhibitory potency.

With the recent announcement of clinical trials with a compstatin analog for the treatment of age-related macular degeneration, another important milestone has been reached on its way to a drug. Furthermore, the release of a co-crystal structure of compstatin with C3c allows a detailed insight into the binding mode and paves the way to the rational design of peptides and mimetics with improved activity. Considering the new incentives and the promising pre-clinical results, compstatin seems to be well equipped for the challenges on its way to a clinical therapeutic.

Compstain acts as protein- protein interaction inhibitor of the onvertase.

Fig.1 Compstain acts as protein-protein interaction inhibitor of the onvertase. (Ricklin, 2009)

Binding Sites of Compstatin to C3

The binding sites are clearly exposed in C3 as well as in their physiologically generated fragments C3b and C3c, which is located within the 40-kDa C-terminal half of the β-chain of C3. The binding sites are buried in native C3 and become available only after the conformational change that occurs upon cleavage of C3 to C3b and C3c. Spontaneous hydrolysis of the thioester of C3 converts native C3 into C3 (H2O). So C3 preparations are actually the mixtures of native C3 and C3(H2O). Binding of compstatin to C3(H2O) is biphasic, whereas that to C3b follows a 1:1 binding model. So, the conformation of the compstatin binding site in C3(H2O) is different from that of C3b.

Structure-Activity Relationships in Compstatin

Oxidation of cysteine residue is required for its functional activity. Because oxidation of cysteine residues maintaining the structure of compstatin is optimal for binding, which preserves its functional activity. The retro-inverso mimetic of compstatin is inactive. So, it appears that binding to C3 is not solely dependent on the side chain interactions and that correctly oriented main-chain atoms also make a contribution to binding. Compstatin contains a type I β-turn encompassing residues Gln5-Gly8, and these residues are important for the inhibitory activity of the peptide. Besides, side-chain interactions exist between some of the turn residues and C3.

Biotransformation of Compstatin

The proteolytic susceptibility of a biologically active peptide is as essential to its biological effect as its affinity for the target protein and its in vivo half-life. The cyclic nature of compstatin is essential not only in stabilizing its structure but also in protecting it from enzymatic processing. Also, compstatin is the first example of a peptide, whose proteolytic processing in blood has been shown to be blocked by cyclization. Acetylation can prevent the N-terminal processing of compstatin (removal of Ile1) and thereby enhance the inhibitory activity of the peptide. The acetylated analog has an inactivation rate of 0.01%/min at 22°C and 0.03%/min at 37°C in serum. So, ac-compstatin is stable against proteolytic cleavage in human blood and has been developed as an in vivo complement inhibitor.

Based on our advanced compstain development services strategy and well-developed complement therapeutic platform, Creative Biolabs is confident in proving customized compstain development services against a variety of complement component, especially for those which are essential for complement activities. Please contact us for more information or a detailed quotation.

1. Ricklin, D. Compstatin: a complement inhibitor on its way to clinical application. Current Topics in Complement II. 2008, 262-281.

For Research Use Only.

Online Inquiry

  • For Research Use Only. Not For Clinical Use.

Contact us


  • Tel:
  • Fax:
  • Email:
  • Global Locations

Follow us on

Copyright © 2021 Creative Biolabs. All Rights Reserved.