Clq受体(ClqR)是新发现的补体调节蛋白。本项目以经典途径始动分子Clq为靶标，采用噬菌体肽库存技术，研制可分别阻断Clq与ClrCls、抗原抗体复合物结合从而抑制补体活化的ClqR模拟短肽，并在动物模型中验证其抗炎作用。意义：（1）为应用新型肽类药物进行抗补体治疗奠定基础；（2）为补体抑制剂的研制探索新途径；（3）在一定程度上揭示ClqR的结?功能关系。

Complement system shows an important role in the first line of defense against infections, but the disorder of its activation can cause diseases. Anti-complement therapy is a very key field in the complement research. Through different regulation pathway have been developed to inhibit the activation of complement, there is still not a satisfactory way which can make reasonable regulation to the activation of complement. In this study, a novel strategy to inhibit the activation of the complement system has been developed. Two phage displayed peptide libraries，Ph.D.-C7CTM Phage Display Peptide Library and Ph.D.-12TM Phage Display Peptide Library, were screened for binders to C1q, the recognition subunit of the classical complement pathway and a panel of C1q-binding clones was isolated. By ELISA analysis and inhibitory assay of C1q-mediated hemolytic activity, 23 positive clones were selected, which had median inhibitory concentrations(IC50) of 2.0~13.2nmol/L. Among them, 15 clones could inhibit the binding of C1q to the C1q receptors(C1qR) on U937 cells or to aggregated immunoglobulin G(AIgG) and the binding of these clones to C1q involved either the collage-like region(CLR) or the globular region(GR) of C1q. A number of similar, but not identical, sets of sequences of C1q-binding clones were identified by DNA sequencing and the deduced amino acid sequences of selected 15 peptides are: HWDPFSLSAYFP(3 with the consensual sequence), LTQHNSPFFLLP(2 with the consensual sequence), WYEGPFTLETWP, TSNPFFLWYPQP, SPAFHPFHMGLA, QTPFQLW, NPFNWTS, SPFXLTS, FLTWLDP, FSTFLYP, GPMWWSY and NPFXLIL。Sequence matches shown that these sequences are not homologous to cC1qR or gC1qR and IgG or IgM, as well as other proteins listed in the Genbank and SwissProt databank. 5 12-mer peptides were synthesized and had very low avidity to C1q, with Kd of 25.0~150.0mmol/L, biological activities and the half-life in animals. These data suggest that these peptides contain the modeling epitopes of C1qR binding with CLR or GR of C1q, or IgG binding with GR of C1q and inhibit the binding and hemolytic activities mediated by C1q and may lead to the development of peptido-mimetics with C1q modulating potential, which are promising leaders for therapeutic inhibitors of the earliest step of the classical complement pathway.