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A small fragment of factor B as a potential inhibitor of complement alternative pathway activity
Enas Yasser Sultan1, Dina Eid Rizk1, Hany Ibrahim Kenawy1
1Department of Microbiology & Immunology, Faculty of Pharmacy, Mansoura University, Egypt.
Background:
The complement system is a key player in innate immunity and a modulator of the adaptive immune system. Among the three pathways of complement, the alternative pathway (AP) accounts for most of the complement activation. Factor B (FB) is a major protease of the AP, making it a promising target to inhibit the AP activity in conditions of uncontrolled complement activation.
Methods:
Based on the data obtained from sequence analysis and conformational changes associated with FB, we expressed and purified a recombinant FB fragment (FBfr). We tested the inhibitory activity of the protein against the AP by in vitro assays.
Results:
FBfr protein was proven to inhibit the complement AP activity when tested by C3b deposition assay and rabbit erythrocyte hemolytic assay.
Conclusion:
Our recombinant FBfr was able to compete with the native human FB, which allowed it to inhibit the AP activity. This novel compound is a good candidate for further characterization and testing to be used in complement diagnostic tests and as a drug lead in the field of complement therapeutics.
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