title: Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a.
abstract: The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the native octapeptide in inhibiting the binding of 125I-labeled anaphylatoxin C5a to human neutrophil membrane receptors. The observed apparent binding Ki's for the compounds (8-10) are in the range of 1-3 microM, and they possess nearly full agonist activity, despite the fact that these analogues are one-eighth or -ninth the size of the natural ligand anaphylatoxin C5a.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.forename: D A
authors.initials: DA
authors.lastname: Quincy
authors.forename: B
authors.initials: B
authors.lastname: Lane
authors.forename: K W
authors.initials: KW
authors.lastname: Mollison
authors.forename: Y S
authors.initials: YS
authors.lastname: Or
authors.forename: J R
authors.initials: JR
authors.lastname: Luly
authors.forename: G W
authors.initials: GW
authors.lastname: Carter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a