Structure-kinetic relationship analysis of the therapeutic complement inhibitor compstatin.

ABSTRACT: Compstatin is a 13-residue peptide that inhibits activation of the complement system by binding to the central component C3 and its fragments C3b and C3c. A combination of theoretical and experimental approaches has previously allowed us to develop analogs of the original compstatin peptide with up to 264-fold higher activity; one of these analogs is now in clinical trials for the treatment of age-related macular degeneration (AMD). Here we used functional assays, surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) to assess the effect of modifications at three key residues (Trp-4, Asp-6, Ala-9) on the affinity and activity of compstatin and its analogs, and we correlated our findings to the recently reported co-crystal structure of compstatin and C3c. The K(D) valu

SUBMITTER: Magotti P 

PROVIDER: S-EPMC2760637 | biostudies-literature | 2009 Nov-Dec

REPOSITORIES: biostudies-literature