ABSTRACT
Complement component C3 is an excellent target for inhibition because it is the convergence point of the classical, lectin, and alternative pathways of complement activation and the starting point of the common pathway. This chapter presents an overview of the discovery of the C3-binding complement inhibitor peptide compstatin and the design of active compstatin analogues. The design of active compstatin analogues is an example of a methodologically integrative, cross-disciplinary, and collaborative approach. Random peptide libraries displayed in phages have proven to be useful tools for large and rapid combinatorial searches for peptides that bind to proteins or monoclonal antibodies. The inhibition of complement activation by compstatin was measured in normal human serum and found to be almost identical to that of the alternative pathway using hemolytic assays. Compstatin has been shown to inhibit in vitro complement activation in human blood, plasma, and serum. It has been shown that compstatin is stable in human blood, plasma, and serum.
