中和C5a过敏毒素的分子设计研究(英文)

Study of molecular design for antagonisting C5a Anaphylatoxin

目的 从蛋白质结构与功能的关系出发，探讨Ｃ５ａＲ与其配体Ｃ５ａ的结合位。方法 按分子设计理论，采用亲水性方案寻打Ｃ５ａ胞外区高亲水性区域，Ｆｍｏｃ方案人工合成Ｃ５ａ第９～３０位氨基酸基序（Ｐ２２肽），经高压液相色谱纯化，毛细管电泳鉴定。结果合成多肽（Ｐ２２）的纯度为９５．１９％，每次缩合的平均效率为９９．７８％；能与ａｎｔｉ－Ｃ５ａＲ ＭｃＡｂ（Ｓ５／Ⅰ，Ｓｅｒｏｔｉｃ公司）有效地结合。

Objective To disc over high hydrophilic profiles of the human C5a receptor(CD88) and the specific highaffinity binding site for its ligand C5a anaphylatoxin form r elationship between the structure and function of the protein and the protein mo lecular design principles. MethodsTh e peptides were synthesized by 431A automatic peptide synthesizer,purified b y high pressure liquid phase chromatography(HPLC) and confirmed by capillary electrophoresis.ResultsThe N-terminus No .9～30 profile of the C5aR (called as P22) could interact wit h anti-C5aR McAb ( S5/1,from Serotic Co.),as determined by ELISA.Furthermore,it could als o inhibit OD490 values remarkably by 10.0 μg/L rhC5a(P<0 .05).In addition,the elevation of cytoplasmic Ca2+ concentrati on induced by 10.0 μg/L rhC5a was inhibited by P22 in dt2cAMP differentiated U937 cells(p<0..01).ConclusionIt is possible that the C5a anaphyla toxin could be removed from the body,and some new types of drug which could be used to treat diseases related to C5a anaphylatoxin could be manufactured.