Design of miniprotein inhibitors targeting complement C9 to block membrane attack complex assembly - PubMed
a day ago
- #protein design
- #immune diseases
- #complement system
- The study focuses on designing mini-protein inhibitors to block complement C9, a key component in the membrane attack complex (MAC) formation, linked to various immune diseases.
- Deep learning-based methods were used for de novo design of mini-protein inhibitors that specifically target and block the membrane insertion of complement C9.
- The designed inhibitors showed high binding affinity (700 pM) and were validated through X-ray crystallography and biochemical studies.
- In vivo tests demonstrated the inhibitors' effectiveness in preventing hemolysis, outperforming existing treatments like eculizumab.
- The inhibitors present a potential therapeutic option for diseases caused by abnormal complement activation.
- A patent application has been filed for the use of these mini-protein inhibitors in hemolysis inhibition.