A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model.

A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model.
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来自 CD2 蛋白 β 链区域的肽,可抑制小鼠模型中的细胞粘附并抑制关节炎。

DOI:
10.1111/j.1747-0285.2010.01001.x
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发表时间:
2010
影响因子:
3
通讯作者:
Latendresse,JohnR
Latendresse,JohnR
中科院分区:
医学4区
文献类型:
--
作者:
Satyanarayanajois,SeetharamaD;Büyüktimkin,Barlas;Gokhale,Ameya;Ronald,Sharon;Siahaan,TerunaJ;Latendresse,JohnR

文献摘要

相似文献

细胞黏附分子在免疫反应的每一步都起着核心作用。白细胞的功能可以通过调节细胞黏附分子之间的黏附相互作用来开发针对自身免疫性疾病的治疗剂。在参与免疫应答的不同细胞黏附分子中,CD2及其配体CD58(LFA-3)是最具代表性的两种介导免疫应答的黏附分子。为了调节细胞间的黏附相互作用,根据CD2蛋白β-链区域的不连续表位设计了多肽。这两条链通过多肽键连接在一起。通过插入β-折叠诱导的Pro-Gly序列和与β结合的CD2蛋白的关键氨基酸序列,在多肽中的CD2链得到核。使用荧光分析,对在细胞黏附中显示潜在抑制活性的多肽进行了评估,以了解它们与CD58蛋白结合的能力。在对接研究的基础上,提出了CD58蛋白与多肽结合的模型。在胶原性关节炎小鼠模型中给予其中一种多肽P3,表明多肽P3能够抑制小鼠的类风湿性关节炎。
Cell adhesion molecules play a central role at every step of the immune response. The function of leukocytes can be regulated by modulating adhesion interactions between cell adhesion molecules to develop therapeutic agents against autoimmune diseases. Among the different cell adhesion molecules that participate in the immunologic response, CD2 and its ligand CD58 (LFA‐3) are two of the best‐characterized adhesion molecules mediating the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the β‐strand region of CD2 protein. The two strands were linked by a peptide bond. β‐Strands in the peptides were nucleated by inserting a β‐sheet‐inducing Pro‐Gly sequence with key amino acid sequences from CD2 protein that binds to CD58. Using a fluorescence assay, peptides that exhibited potential inhibitory activity in cell adhesion were evaluated for their ability to bind to CD58 protein. A model for peptide binding to CD58 protein was proposed based on docking studies. Administration of one of the peptides, P3 in collagen‐induced arthritis in the mouse model, indicated that peptide P3 was able to suppress rheumatoid arthritis in mice.