ANTAGONISTIC PEPTIDES AGAINST HUMAN ANAPHYLATOXIN C5A

Multivalent synthetic peptides derived from C5a were prepared in order to examine their effects on the C5a receptor (CSaR). Multiple antigen peptide (MAP) of the C5a C-terminal region (MAP(61-74)) bound to cell s expressing CSaR with high affinity. On the other hand, N-terminal pe ptides (MAP(3-16) and MAP(12-26)) and one with a sequence from the mid -portion of C5a (MAP(37-53)) did not bind to the cells. In addition, M AP(61-74) inhibited Ca2+ mobilization and release of beta-hexosaminida se by C5a from dibutyryl cAMP-activated U937 cells. This Ca2+ mobiliza tion was also inhibited by MAP(12-26) and Mono(61-74), the monomeric C -terminal peptide. Taken together, these data indicate that C5a binds to the CSaR via its C-terminal region. Furthermore, MAP(61-74), a 14me r peptide that has additional amino acids at the N-terminal compared w ith the C-terminal octapaptide, can bind to CSaR and can be considered an antagonist of C5a which may prove useful as an agent for controlli ng the allergic response caused by complement activation.