Design and biological activity of a new generation of synthetic C3a analogues by combination of peptidic and non-peptidic elements.
Based on published X-ray crystallographic data of the anaphylatoxic complement peptide C3a, we have synthesized a series of peptides with appropriate amino acid exchanges and a maximal length of 13 amino acids. N-terminal acylation of these optimized structures with epsilon-aminohexanoic acid and complex aromatic structures like fluorenylmethoxycarbonyl, 2-nitro-4-azidophenyl, fluoresceinyl and rhodaminyl leads to a dramatic increase in biological activity. The culmination of our synthetic efforts is a C3a analogue with 13 amino acid residues and a biological activity six times that of native C3a.
Gerardy-Schahn
R
R
Institut für Medizinische Mikrobiologie, Universität Mainz, F.R.G.
Ambrosius
D
D
Casaretto
M
M
Grötzinger
J
J
Saunders
D
D
Wollmer
A
A
Brandenburg
D
D
Bitter-Suermann
D
D
D000255:Adenosine Triphosphate / Q000097:blood; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002412:Cations; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D002412:Cations; D003176:Complement C3; D010455:Peptides; D015926:Complement C3a; D000255:Adenosine Triphosphate