Identification of a Receptor-Binding Region in the Core Segment of the Human Anaphylatoxin C5a

• Published in: Journal of medicinal chemistry 1994-08, Vol.37 (17), p.2783-2790
• Main Authors: Vlattas, Isidoros, Sytwu, Iou Iou, Dellureficio, James, Stanton, James, Braunwalder, Albert F, Galakatos, Nicholas, Kramer, Richard, Seligmann, Bruce, Sills, Matthew A, Wasvary, James
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Arginine; Binding Sites; Biological and medical sciences; Cell Membrane - metabolism; Complement; Complement C5a - chemistry; Complement C5a - metabolism; Disulfides; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Kinetics; Models, Structural; Molecular immunology; Molecular Sequence Data; Neutrophils - metabolism; Peptides - chemical synthesis; Peptides - metabolism; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - metabolism; Protein Structure, Secondary; Receptor, Anaphylatoxin C5a; Receptors, Complement - metabolism
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00043a017

In order to identify regions of C5a that contribute to receptor binding and functional activity of the anaphylatoxin, a series of peptides was synthesized in which core segments have been attached to C-terminal segments via native peptidic or disulfide bonds. It has been found that residues Arg40 and Arg46 in the loop-3 region of the core induce a 1000-fold increase in the affinity of the disordered C-terminal segment of C5a. The results obtained from this work lead to the conclusion that the loop-3 region is most likely the core binding site of C5a.