Evaluation of the C-terminal C5a effector site with short synthetic C5a analog peptides.
Biological activities have been determined for a series of 18 peptides based on the C-terminal sequence of human or rat C5a. Lysosomal enzyme release was tested in two cell types, the promyelotic leukemia cell line U937 and polymorphonuclear leukocytes. In addition, an ATP-release assay with guinea pig platelets was performed. It was demonstrated that the C-terminal octapeptide 67-74 of human C5a represents the minimal sequence required to induce a measurable biological signal in all assays. Extending this peptide to a length of 21 amino acids produced at best only a slight enhancement of potency. Amino acid replacements with either tryptophanyl or phenylalanyl residues in positions between 65-69 either increased potency (at position 67), or abrogated potency (at position 66) in the two lysosomal enzyme assays. N-terminal acylation with the fluorenylmethoxy-carbonyl-aminohexanoyl group slightly enhanced C5a potency. In desensitization experiments with guinea pig platelets all peptides with a C5a activity were able to desensitize not only the C5a but also the C3a responses.
Köhl
J
J
Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, FRG.
Lübbers
B
B
Klos
A
A
Bautsch
W
W
Casaretto
M
M
D000118:Acetylglucosaminidase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D015936:Complement C5a / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D015936:Complement C5a; D000255:Adenosine Triphosphate; D009195:Peroxidase; D000118:Acetylglucosaminidase