Antagonistic peptides against human anaphylatoxin C5a.

Multivalent synthetic peptides derived from C5a were prepared in order to examine their effects on the C5a receptor (C5aR). Multiple antigen peptide (MAP) of the C5a C-terminal region (MAP61-74) bound to cells expressing C5aR with high affinity. On the other hand, N-terminal peptides (MAP3-16 and MAP12-26) and one with a sequence from the mid-portion of C5a (MAP37-53) did not bind to the cells. In addition, MAP61-74 inhibited Ca2+ mobilization and release of beta-hexosaminidase by C5a from dibutyryl cAMP-activated U937 cells. This Ca2+ mobilization was also inhibited by MAP12-26 and Mono61-74, the monomeric C-terminal peptide. Taken together, these data indicate that C5a binds to the C5aR via its C-terminal region. Furthermore, MAP61-74, a 14mer peptide that has additional amino acids at the N-terminal compared with the C-terminal octapaptide, can bind to C5aR and can be considered an antagonist of C5a which may prove useful as an agent for controlling the allergic response caused by complement activation.