Inhibition by various peptides of the activation of C1, the first component of complement, and the interaction of C gamma 2 domain of IgG with C1q.
Three groups of peptides were synthesized, each of which was proposed to be a part of the C1q binding sites of the C gamma 2 domain of IgG. They were: Trp(277)-Tyr-Val-Asp-Gly (WYVDG), Thr(289)-Lys-Pro-Arg (tuftsin) and Gly(316)-Lys-Glu-Tyr-Lys (GKEYK) or portions of these peptides. Assays included CH50, consumption of serum complement induced by heat-aggregated IgG, C1 hemolysis and an enzyme immunoassay that directly measures interaction between C1q and IgG. Peptides near Gly(316) such as GKEY, GKE or EYK inhibited CH50 and heat-aggregated IgG-induced consumption of serum complement. WYVDG also inhibited CH50, with 50% inhibition at 2.05 mM, which was more than the concentrations of peptides near Gly(316) at 50% inhibition. Tuftsin was only slightly inhibitory in both systems. Results of C1 hemolysis indicated that dipeptides composed of two aromatic amino acids, especially Trp-Tyr, were more inhibitory than dipeptides of which one residue was an aromatic amino acid. Peptides such as EYK, GKEY or GKE were very inhibitory, and tuftsin was far less inhibitory than these peptides in C1 hemolysis. Results of enzyme immunoassay also showed that dipeptides composed of two aromatic amino acids were more inhibitory than dipeptides of which one residue was aromatic amino acid. WYVDG was most inhibitory in enzyme immunoassay, but tuftsin, EYK, GKEY GKE and KE were less effective.
D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D015922:Complement C1q; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*
D003174:Complement C1 Inactivator Proteins; D007074:Immunoglobulin G; D010455:Peptides; D015922:Complement C1q; D003166:Complement Activating Enzymes