Identification and synthesis of a receptor binding site of human anaphylatoxin C5a.
C5a is a 74 amino acid polypeptide that likely plays an important role in the pathogenesis of a number of inflammatory diseases. Therefore, the discovery of a C5a antagonist is of considerable therapeutic interest. A series of peptides designed to survey various regions of the molecule was synthesized by solid-phase peptide synthesis and evaluated for receptor-binding activity with polymorphonuclear leukocyte membranes. The C-terminal octapeptide (Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) was identified as the smallest fragment which possessed reasonable C5a receptor binding activity.
Kawai
M
M
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Quincy
D A
DA
Lane
B
B
Mollison
K W
KW
Luly
J R
JR
Carter
G W
GW
D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D011951:Receptors, Complement; C069791:acetylhistidyl-lysyl-aspartyl-methionyl-glutaminyl-leucyl-glycyl-arginine; D015936:Complement C5a