• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International Journal of Peptide Research and Therapeutics >Drug Development-targeted Screening of Leptin Agonist Glycopeptides
【24h】

Drug Development-targeted Screening of Leptin Agonist Glycopeptides

机译：瘦素激动剂糖肽的药物开发靶向筛选

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

A glycosylated dodecapeptide fragment corresponding to the hypothalamus-active cytokine leptin exhibits agonistic properties to the leptin receptor (ObR) in vitro and penetrates into the brain in vivo. In order to characterize the drug development potential of the lead peptide and to optimize it for pharmacological applicability, a series of biochemical screening assays were custom-tailored to the leptin/ObR system. To identify peptides that bind the extracellular domain of ObR, we characterized the optimal conditions for an ELISA-type assay where the leptin fragments were immobilized to the plates. With this technology we could identify low-dose binder peptidomimetics which, according to a comparison of the conventional cell proliferation assay and a measure of metabolically active cells, revealed that agonists identified by these cellular assays may not necessarily induce the expected growth characteristics in ObR expressing cells. The original glycopeptide lead displayed a 2 h half life in 25% diluted mouse serum but poor stability in mouse brain extract. Fifteen percent of the glycopeptide crossed a dual endothelial/astrocyte cell layer (representing an in vitro model of blood-brain-barrier) in 30 min, and the coexistence of the two cell types appeared necessary to quantify the level of brain accessibility. Finally, in an in vivo mouse model, a Cy5.5 labeled glycopeptide was more evenly distributed all over the body, including the brain, than a similarly labeled full-sized leptin protein.
机译：对应于下丘脑活性细胞因子瘦素的糖基化十二肽片段在体外对瘦素受体（ObR）表现出激动作用，并在体内渗透到大脑中。为了表征先导肽的药物开发潜力并优化其在药理学上的适用性，针对瘦蛋白/ ObR系统量身定制了一系列生化筛选分析方法。为了鉴定结合ObR胞外域的肽，我们表征了瘦素片段固定在平板上的ELISA类型测定的最佳条件。借助这项技术，我们可以鉴定出低剂量的结合剂拟肽，根据常规细胞增殖测定法和代谢活性细胞的测定方法，它们揭示了通过这些细胞测定法鉴定出的激动剂不一定能诱导ObR表达的预期生长特征。细胞。原始糖肽铅在25％稀释的小鼠血清中显示2小时半衰期，但在小鼠脑提取物中的稳定性较差。 15％的糖肽在30分钟内穿过内皮/星形胶质细胞双细胞层（代表血脑屏障的体外模型），两种细胞类型的共存似乎是量化大脑可及性水平所必需的。最后，在体内小鼠模型中，Cy5.5标记的糖肽比类似标记的全尺寸瘦素蛋白更均匀地分布在整个身体，包括大脑。

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