A new generation of potent complement inhibitors of the Compstatin family |
| |
Authors: | López de Victoria Aliana Gorham Ronald D Bellows-Peterson Meghan L Ling Jun Lo David D Floudas Christodoulos A Morikis Dimitrios |
| |
Institution: | Department of Bioengineering and Center for Bioengineering Research, University of California, Riverside, CA 92521, USA. |
| |
Abstract: | Compstatin family peptides are potent inhibitors of the complement system and promising drug candidates against diseases involving under-regulated complement activation. Compstatin is a 13-residue cyclized peptide that inhibits cleavage of complement protein C3, preventing downstream complement activation. We present three new compstatin variants, characterized by tryptophan replacement at positions 1 and/or 13. Peptide design was based on physicochemical reasoning and was inspired by earlier work, which identified tryptophan substitutions at positions 1 and 13 in peptides with predicted C3c binding abilities Bellows M.L., Fung H.K., Taylor M.S., Floudas C.A., López de Victoria A., Morikis D. (2010) Biophys J; 98: 2337-2346]. The new variants preserve distinct polar and nonpolar surfaces of compstatin, but have altered local interaction capabilities with C3. All three peptides exhibited potent C3 binding by surface plasmon resonance and potent complement inhibition by enzyme-linked immunosorbent assay. We also present enzyme-linked immunosorbent assay data and detailed surface plasmon resonance kinetic data of three peptides from previous computational design. |
| |
Keywords: | complement system complement system inhibitors compstatin family peptide design structure‐based drug design |
本文献已被 PubMed 等数据库收录! |
|