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Structure-kinetic Relationship Analysis of the Therapeutic Complement Inhibitor Compstatin by Paola Magotti; Daniel Ricklin; Hongchang Qu; You-Qiang Wu; Yiannis N. Kaznessis; John D. Lambris is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Structure-kinetic Relationship Analysis of the Therapeutic Complement Inhibitor Compstatin about?
## 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__~ values for the panel of tested analogs ranged from 10^−6^ to 10^−8^ M. These differences in binding affinity could be attributed mainly to differences in dissociation rather than association rates, with a >4‐fold range in __k__~on~ values (2–10 × 10^5^ M^−1^ s^−1^) and a __k__~off~ variation of >35‐fold (1–37 × 10^−2^ s^−1^) being observed. The stability of the C3b‐compstatin compl
Who reads Structure-kinetic Relationship Analysis of the Therapeutic Complement Inhibitor Compstatin?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Paola Magotti; Daniel Ricklin; Hongchang Qu; You-Qiang Wu; Yiannis N. Kaznessis; John D. Lambris
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0952-3499)
- Published
- 2009
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)