具C1q抑制活性的C1q结合环七肽的研究
发布时间：2019-05-21 10:16
【摘要】：补体系统是天然免疫的重要组成部分，在机体免疫防御、免疫调节中起重要作用。然而，补体的异常活化也参与许多疾病的发生和发展，因此抗补体治疗一直是补体学研究中的重要领域之一。补体级联反应中的多个环节都可作为抗补体治疗的靶点。C1q不仅是补体经典途径的始动识别因子，它还能与多种配基相互作用，产生多种生物功能，其中与免疫复合物(immune complex，IC)及C1q受体(C1q receptor，C1qR)的结合所引发的后续反应就参与多种疾病中补体介导的组织损伤。我们设想，选择性抑制C1q与IC及C1qR的结合，可能有效阻断补体异常激活介导的组织损伤。 本研究中，我们以C1q为靶标筛选噬菌体展示环七肽库，获得一批结合C1q并具C1q抑制活性的噬菌体克隆，然后根据噬菌体展示肽DNA序列人工合成短肽并研究合成短肽及其BSA偶联物的活性。 一、C1q结合性噬菌体克隆的筛选与鉴定 以人C1q为钓饵筛选噬菌体环七肽库，经C1q结合实验、U937细胞C1qR结合抑制实验、多聚IgG(aggregated immunoglobulin G，AIgG)竞争抑制实验鉴定噬菌体克隆，获得一批结合C1q并具C1q抑制活性的噬菌体克隆，，从其展示肽DNA测序结果推导氨基酸顺序，得到8个序列：CKKSGKPKC、CFNPFRLDC、CWDLFLFPC，CSPFFLTPC、CSPFHLEPC、CWGNPFFLC、CNNPFTLLC和CSPFFWYEC。
[Abstract]:The complement system is an important part of natural immunity, and plays an important role in the immune defense and immune regulation of the body. However, the abnormal activation of complement is involved in the occurrence and development of many diseases, so the anti-complement therapy has been one of the important fields in the complement study. A plurality of links in the complement cascade reaction can be used as a target for anti-complement therapy. C1q is not only the initial recognition factor of the complement classical pathway, but also can interact with a variety of ligands to produce a variety of biological functions, in which an immune complex (IC) and a C1q receptor (C1q receptor, The subsequent reaction initiated by the binding of C1qR is involved in the complement-mediated tissue damage in a variety of diseases. It is envisaged that the selective inhibition of the binding of C1q to the IC and C1qR may effectively block complement anomaly activation-mediated tissue damage. In this study, we screened the phage display loop 7 peptide library with C1q as the target to obtain a batch of phage clones with C1q and C1q inhibitory activity, and then artificially synthesized the short peptides according to the phage display peptide DNA sequence and studied the synthetic short peptides and the synthesis of the short peptides. The activity of its BSA conjugate. 1. The screening and identification of the CC1q binding phage clone and the identification of human C1q as the bait for screening the phage-cyclic heptapeptide library. The C1q binding assay, the U937 cell C1qR binding inhibition assay, the polyIgG (aggregated im) Funglobulin G (AIgG) competition inhibition assay, phage clones were identified, a batch of phage clones binding to C1q and having C1q inhibitory activity were obtained, and the amino acid sequence was derived from the results of their presentation of peptide DNA sequencing to give 8 sequences: CKKSGKPKC, CFNPFRLDC, CWDLFFIPC, CSPFFLTPC, CSPFHLE
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392
本文编号：2482025
[Abstract]:The complement system is an important part of natural immunity, and plays an important role in the immune defense and immune regulation of the body. However, the abnormal activation of complement is involved in the occurrence and development of many diseases, so the anti-complement therapy has been one of the important fields in the complement study. A plurality of links in the complement cascade reaction can be used as a target for anti-complement therapy. C1q is not only the initial recognition factor of the complement classical pathway, but also can interact with a variety of ligands to produce a variety of biological functions, in which an immune complex (IC) and a C1q receptor (C1q receptor, The subsequent reaction initiated by the binding of C1qR is involved in the complement-mediated tissue damage in a variety of diseases. It is envisaged that the selective inhibition of the binding of C1q to the IC and C1qR may effectively block complement anomaly activation-mediated tissue damage. In this study, we screened the phage display loop 7 peptide library with C1q as the target to obtain a batch of phage clones with C1q and C1q inhibitory activity, and then artificially synthesized the short peptides according to the phage display peptide DNA sequence and studied the synthetic short peptides and the synthesis of the short peptides. The activity of its BSA conjugate. 1. The screening and identification of the CC1q binding phage clone and the identification of human C1q as the bait for screening the phage-cyclic heptapeptide library. The C1q binding assay, the U937 cell C1qR binding inhibition assay, the polyIgG (aggregated im) Funglobulin G (AIgG) competition inhibition assay, phage clones were identified, a batch of phage clones binding to C1q and having C1q inhibitory activity were obtained, and the amino acid sequence was derived from the results of their presentation of peptide DNA sequencing to give 8 sequences: CKKSGKPKC, CFNPFRLDC, CWDLFFIPC, CSPFFLTPC, CSPFHLE
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392
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