Sequence recognition of alpha-LFA-1-derived peptides by ICAM-1 cell receptors: inhibitors of T-cell adhesion.
Sequence recognition of alpha-LFA-1-derived peptides by ICAM-1 cell receptors: inhibitors of T-cell adhesion.
复制标题
ICAM-1 细胞受体对 α-LFA-1 衍生肽的序列识别：T 细胞粘附抑制剂。
DOI：
10.1111/j.1747-0285.2007.00549.x
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发表时间：
2007
影响因子：
3
通讯作者：
Siahaan,TerunaJ
中科院分区：
文献类型：
--
作者：
Yusuf-Makagiansar,Helena;Yakovleva,TatyanaV;Tejo,BimoA;Jones,Karen;Hu,Yongbo;Verkhivker,GennadyM;Audus,KennethL;Siahaan,TerunaJ
阻断细胞间黏附分子-1/白细胞功能相关抗原-1(Signal-2)相互作用的T细胞黏附信号可以抑制自身免疫性疾病(如1型糖尿病、银屑病)的进展，防止同种异体排斥反应。在本研究中，我们通过合成和评价六肽抑制T细胞黏附的生物活性，确定了cLAB.L肽的活性区域(S)[clo(1，12)Pen-ITDGEATDSGC]。还建立了一种新的异型T细胞黏附实验，为研究肺部炎症过程中T细胞黏附过程提供了一个模型。两个六肽，ITDGEA和DGEATD，被发现比其他线性六肽更有活性。ITDGEA的环衍生物[即Cyclo(1，6)ITDGEA]的活性与母体线状多肽相似，但活性低于cLAB.L多肽。计算结合实验解释了这些多肽与细胞间黏附分子-1结合的可能机制。ITDGEA和DGEATD都结合在细胞间黏附分子-1上的同一位置，它们与细胞间黏附分子-1的D_1上的Gln34和Gln73残基相互作用。未来将通过对多肽与细胞间黏附分子-1的结构和结合的研究来设计更有效的Cyclo(1，6)ITDGEA的衍生物。异型T细胞与CALU-3的黏附也将被用作另一种测试来评估所设计的多肽的选择性。
Blocking the T‐cell adhesion signal from intercellular adhesion molecule‐1/leukocyte function‐associated antigen‐1 interactions (Signal‐2) can suppress the progression of autoimmune diseases (i.e. type‐1 diabetes, psoriasis) and prevent allograph rejection. In this study, we determined the active region(s) of cLAB.L peptide [cyclo(1,12)Pen‐ITDGEATDSGC] by synthesizing and evaluating the biologic activity of hexapeptides in inhibiting T‐cell adhesion. A new heterotypic T‐cell adhesion assay was also developed to provide a model for the T‐cell adhesion process during lung inflammation. Two hexapeptides, ITDGEA and DGEATD, were found to be more active than the other linear hexapeptides. The cyclic derivative of ITDGEA [i.e. cyclo(1,6)ITDGEA] has similar activity than the parent linear peptide and has lower activity than cLAB.L peptide. Computational‐binding experiments were carried out to explain the possible mechanism of binding of these peptides to intercellular adhesion molecule‐1. Both ITDGEA and DGEATD bind the same site on intercellular adhesion molecule‐1 and they interact with the Gln34 and Gln73 residues on D1 of intercellular adhesion molecule‐1. In the future, more potent derivatives of cyclo(1,6)ITDGEA will be designed by utilizing structural and binding studies of the peptide to intercellular adhesion molecule‐1. The heterotypic T‐cell adhesion to Calu‐3 will also be used as another assay to evaluate the selectivity of the designed peptides.