Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 12, Pages 7116-7124Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000200
Keywords
-
Categories
Funding
- Department of Biotechnology, New Delhi, India
Ask authors/readers for more resources
Complement factor B (fB) is a key constituent of the alternative pathway (AP). Its central role in causing inflammation and tissue injury through activation of the AP urges the need for its therapeutic targeting. In the current study, we have screened phage-displayed random peptide libraries against fB and identified a novel cyclic hendecapeptide that inhibits activation of fB and the AP. Structure-activity studies revealed that: 1) the cysteine-constrained structure of the peptide is essential for its activity; 2) Ile(5), Arg(6), Leu(7), and Tyr(8) contribute significantly to its inhibitory activity; and 3) retro-inverso modification of the peptide results in loss of its activity. Binding studies performed using surface plasmon resonance suggested that the peptide has two binding sites on fB, which are located on the Ba and Bb fragments. Studies on the mechanism of inhibition revealed that the peptide does not block the interaction of fB with the activated form of C3, thereby suggesting that the peptide inhibits fB activation primarily by inhibiting its cleavage by factor D. The peptide showed a weak effect on preformed C3 and C5 convertases. Like inhibition of fB cleavage, the peptide also inhibited C2 cleavage by activated C1s and activation of the classical as well as lectin pathways. Based on its inhibitory activities, we named the peptide Complin. The Journal of Immunology, 2010, 184: 7116-7124.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available