Oxazole-modified glycopeptides that target arthritis-associated class II MHC Aq and DR4 proteins
Oxazole-modified glycopeptides that target arthritis-associated class II MHC Aq and DR4 proteins
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DOI：
10.1039/c003640d
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Linusson, Anna
中科院分区：
文献类型：
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作者：
Andersson, Ida E.;Batsalova, Tsvetelina;Linusson, Anna
糖肽CII 259 -273是来自II型胶原（CII）的片段，可以在对胶原诱导的关节炎（CIA）易感的小鼠中诱导耐受，CIA是类风湿性关节炎（RA）的经验证的疾病模型。在这里，我们描述了一个小系列的修改CII 259 -273糖肽的设计和合成与恶唑杂环取代三个潜在的不稳定的肽键。评价这些糖肽模拟物与鼠CIA相关A（q）和人RA相关DR 4 II类主要组织相容性复合体（MHC）蛋白的结合。恶唑修饰大大减少或完全消除与A（q）的结合。然而，两种糖肽模拟物在与DR 4结合时耐受良好，并且它们还通过一种或两种DR 4限制性T细胞杂交瘤诱导强烈的应答。这项工作有助于开发一种用于诱导CIA免疫耐受的糖肽，其长期目标是开发一种治疗RA的治疗性疫苗。
The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA). Here, we describe the design and synthesis of a small series of modified CII259-273 glycopeptides with oxazole heterocycles replacing three potentially labile peptide bonds. These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins. The oxazole modifications drastically reduced or completely abolished binding to A(q). Two of the glycopeptidomimetics were, however, well tolerated in binding to DR4 and they also induced strong responses by one or two DR4-restricted T-cell hybridomas. This work contributes to the development of an altered glycopeptide for inducing immunological tolerance in CIA, with the long-term goal of developing a therapeutic vaccine for treatment of RA.