Reevaluation of the C3a active site using short synthetic C3a analogues
- 1 July 1990
- journal article
- Published by Wiley in European Journal of Immunology
- Vol. 20 (7), 1463-1468
- https://doi.org/10.1002/eji.1830200709
Abstract
In 1980 the C‐terminal pentapeptide LGLAR (C3a 73–77) was described (Caporale, L. H. et al. J. Biol. Chem. 1980. 255: 10758) as the minimal sequence inducing a C3a‐specific activity. We have synthesized C3a‐analogue peptides connected to non‐peptidic acyl residues known to potentiate biological activity. Starting from the acylated hexapeptide fluorenylmethoxycarbonyl(Fmoc)‐aminohexanoyl(Ahx)‐ALGLAR, a related series of shorter peptides was synthesized. C3a‐specific activity was measured as ATP release from guinea pig platelets. Even the tripeptide LAR, acylated with Fmoc‐Ahx, exhibited C3a‐specific activity. With 0.34% C3a activity, it was even more potent than the native LGLAR sequence which has 0.01% activity. N‐terminal extension of the acylated tripeptide LAR by adding one to three alanines increased activity tenfold up to 3.26% (Fmoc‐Ahx‐AAALAR), while N‐terminal addition of three glycine residues (Fmoc‐Ahx‐GGGLAR) only increased activity to 0.83% of native C3a. Furthermore, a stimulus‐specific desensitization could be observed. Fmoc‐Ahx‐R and Fmoc‐Ahx‐AR exhibited neither activity nor desensitizing capacity, but the addition of four alanines to the dipeptide AR led to a sequence (Fmoc‐Ahx‐AAAAAR) with a C3a‐specific activity of 0.14%. Even arginine prolonged N‐terminally with five glycines (Fmoc‐Ahx‐GGGGGR) exhibited some C3a‐specific activity so that for biological activity only the appropriate presentation of arginine seems to be essential.Keywords
This publication has 21 references indexed in Scilit:
- Characterization of C3a receptor‐proteins on guinea pig platelets and human polymorphonuclear leukocytesEuropean Journal of Immunology, 1989
- Peptide Analogues of the Anaphylatoxin C3a; Syntheses and PropertiesBiological Chemistry Hoppe-Seyler, 1989
- Structure and function of the anaphylatoxinsSpringer Seminars in Immunopathology, 1984
- Low zone desensitization: a stimulus-specific control mechanism of cell response. Investigations on anaphylatoxin-induced platelet secretion.The Journal of Experimental Medicine, 1982
- Further studies on the use of multi-substituted benzenesulfonyl groups for protection of the guanidino function of arginine.CHEMICAL & PHARMACEUTICAL BULLETIN, 1981
- Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a)Biochemistry, 1978
- Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidaseJCI Insight, 1970
- 9-Fluorenylmethoxycarbonyl function, a new base-sensitive amino-protecting groupJournal of the American Chemical Society, 1970
- ISOLATION OF A FRAGMENT (C3a) OF THE THIRD COMPONENT OF HUMAN COMPLEMENT CONTAINING ANAPHYLATOXIN AND CHEMOTACTIC ACTIVITY AND DESCRIPTION OF AN ANAPHYLATOXIN INACTIVATOR OF HUMAN SERUMThe Journal of Experimental Medicine, 1969
- Platelet Sequestration in Man. I. Methods*JCI Insight, 1964