Peptide analogues of the anaphylatoxin C3a; syntheses and properties.
The chemical syntheses of C-terminally shortened analogues of C3a, which is the best investigated anaphylatoxin and derives from the third component of complement system, is reported. The peptide assembly was performed with the solid-phase technique using a polyamide support and an orthogonal protection strategy. The base-labile Fmoc group was chosen for N alpha protection in combination with acid-labile side-chain protection. Excellent acylation yields could be obtained using HBTU (O-benzotriazolyl-N,N,N',N'-tetramethyluronium hexafluorophosphate) as activating reagent. With this methodology we synthesized eighteen different peptides with the following modifications: Varying the peptide length by sequential addition of glycine or arginine residues, prolongating the N-terminus with the Fmoc- or Fmoc-aminohexanoyl residues and exchanging the glycine in position 74 for alanine or D-alanine. We obtained two C3a analogues, Fmoc-YRAAALALAR and Fmoc-Ahx-YRRGRAAALGLAR, which were shown to be substantially more active than native C3a in the guinea-pig-platelet assay.
Ambrosius
D
D
Deutsches Wollforschungsinstitut Aachen.
Casaretto
M
M
Gerardy-Schahn
R
R
Saunders
D
D
Brandenburg
D
D
Zahn
H
H
D000596:Amino Acids / Q000032:analysis; D000706:Anaphylatoxins / Q000032:analysis* / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003176:Complement C3 / Q000032:analysis*; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis* / Q000138:chemical synthesis / Q000302:isolation & purification
D000596:Amino Acids; D000706:Anaphylatoxins; D003176:Complement C3; D010455:Peptides