具C1q抑制活性的C1q結(jié)合環(huán)七肽的研究
發(fā)布時(shí)間：2019-05-21 10:16
【摘要】：補(bǔ)體系統(tǒng)是天然免疫的重要組成部分，在機(jī)體免疫防御、免疫調(diào)節(jié)中起重要作用。然而，補(bǔ)體的異�；罨矃⑴c許多疾病的發(fā)生和發(fā)展，因此抗補(bǔ)體治療一直是補(bǔ)體學(xué)研究中的重要領(lǐng)域之一。補(bǔ)體級(jí)聯(lián)反應(yīng)中的多個(gè)環(huán)節(jié)都可作為抗補(bǔ)體治療的靶點(diǎn)。C1q不僅是補(bǔ)體經(jīng)典途徑的始動(dòng)識(shí)別因子，它還能與多種配基相互作用，產(chǎn)生多種生物功能，其中與免疫復(fù)合物(immune complex，IC)及C1q受體(C1q receptor，C1qR)的結(jié)合所引發(fā)的后續(xù)反應(yīng)就參與多種疾病中補(bǔ)體介導(dǎo)的組織損傷。我們?cè)O(shè)想，選擇性抑制C1q與IC及C1qR的結(jié)合，可能有效阻斷補(bǔ)體異常激活介導(dǎo)的組織損傷。 本研究中，我們以C1q為靶標(biāo)篩選噬菌體展示環(huán)七肽庫，獲得一批結(jié)合C1q并具C1q抑制活性的噬菌體克隆，然后根據(jù)噬菌體展示肽DNA序列人工合成短肽并研究合成短肽及其BSA偶聯(lián)物的活性。 一、C1q結(jié)合性噬菌體克隆的篩選與鑒定 以人C1q為釣餌篩選噬菌體環(huán)七肽庫，經(jīng)C1q結(jié)合實(shí)驗(yàn)、U937細(xì)胞C1qR結(jié)合抑制實(shí)驗(yàn)、多聚IgG(aggregated immunoglobulin G，AIgG)競爭抑制實(shí)驗(yàn)鑒定噬菌體克隆，獲得一批結(jié)合C1q并具C1q抑制活性的噬菌體克隆，，從其展示肽DNA測序結(jié)果推導(dǎo)氨基酸順序，得到8個(gè)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
【學(xué)位授予單位】：第一軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392
本文編號(hào)：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
【學(xué)位授予單位】：第一軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392
【參考文獻(xiàn)】
相關(guān)期刊論文 前3條
1 武婕,陳惠鵬;噬菌體肽庫研究進(jìn)展[J];軍事醫(yī)學(xué)科學(xué)院院刊;2000年01期
2 譚艷,陳政良;C1q結(jié)合十二肽的活性研究[J];免疫學(xué)雜志;2004年06期
3 白云，朱錫華;微量補(bǔ)體反應(yīng)性溶血測定法[J];免疫學(xué)雜志;1994年02期
本文編號(hào)：2482025
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