...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prevention of passively transferred experimental autoimmune myasthenia aravis by a phage library-derived cyclic peptide
【24h】

Prevention of passively transferred experimental autoimmune myasthenia aravis by a phage library-derived cyclic peptide

机译：噬菌体文库衍生的环肽预防被动转移的实验性自身免疫性重症肌无力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Many pathogenic antibodies in myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are directed against the main immunogenic region (MlR) of the acetylcholine receptor (AcChoR). These antibodies are highly con formation de- pendent: hence, linear peptides derived from native receptor sequences are poor candidates for their immunoneutralization. We employed a phage-epitope library to identify peptide-mimotopes capable of preventing the pathogenicity of the anti-MIR mAb 198. We identified a 15-mer peptide (PMTLPENYFSERPYH) that binds specifically to mAb 198 and inhibits its binding to AcChoR. A 10-fold increase in the affinity of this peptide was achieved by incorpo- rating flanking amino acid residues from the coat protein as present in the original phage library. This extended peptide (AEP- MTLPENYFSERPYHPPPP) was constrained by the addition of cys- teine residues on both ends of the peptide, thus generating a cyclic peptide that inhibited the binding of mAb 198 to AcChoR with a potency that is three orders of magnitude higher when compared with the parent library peptide. This cyclic peptide inhibited the in de binding of mAb 198 to AcChoR and prevented the antigenic modulation of AcChoR caused by mAb 198 in human muscle cell cultures. The cyclic peptide also reacted with several other anti-MlR mAbs and the sera of EAMG rats. ln addition. this peptide blocked the ability of mAb 198 to passively transfer EAMG in rats. Further derivatization of the cyclic peptide may aid in the design of suitable synthetic mimotopes for modulation of MG.
机译：重症肌无力（MG）及其动物模型实验性自身免疫性MG（EAMG）中的许多致病性抗体均针对乙酰胆碱受体（AcChoR）的主要免疫原性区域（M1R）。这些抗体高度依赖构象：因此，源自天然受体序列的线性肽对其免疫中和作用较差。我们使用噬菌体表位文库来鉴定能够预防抗MIR mAb 198致病性的肽模拟物。我们鉴定了一种15肽肽（PMTLPENYFSERPYH），该肽与mAb 198特异性结合并抑制其与AcChoR的结合。通过掺入原始噬菌体文库中存在的外壳蛋白侧翼氨基酸残基，可以使这种肽的亲和力提高10倍。这种延伸的肽段（AEP-MTLPENYFSERPYHPPPP）在肽段的两端均添加了半胱氨酸残基，从而产生了一种环状肽段，可抑制mAb 198与AcChoR的结合，效力高出三个数量级。与亲本文库肽相比。该环状肽抑制了mAb 198与AcChoR的脱结合，并防止了由mAb 198在人肌肉细胞培养物中引起的对AcChoR的抗原调节。环状肽还与其他几种抗MlR mAb和EAMG大鼠的血清反应。 ln。该肽阻断了mAb 198在大鼠中被动转移EAMG的能力。环肽的进一步衍生化可以帮助设计用于调节MG的合适的合成模拟表位。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号