• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Reviews in Molecular Biotechnology >'Anticalins': a new class of engineered ligand-binding proteins with antibody-like properties
【24h】

'Anticalins': a new class of engineered ligand-binding proteins with antibody-like properties

机译：'Anticalins'：具有抗体样特性的新型工程化配体结合蛋白

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

The development of soluble receptor proteins that recognise given target molecules -- ranging from small chemical compounds to macromolecular structures at a cell surface, for example -- is of ever increasing importance in the life sciences and biotechnology. For the past century this area of application was dominated by antibodies, which were traditionally generated via immunisation of animals but have recently also become available by means of protein engineering methods. The so-called 'anticalins' offer an alternative type of ligand-binding proteins, which has been constructed on the basis of lipocalins as a scaffold. The central element of this protein architecture is a #beta#-barrel structure of eight antiparallel strands, which supports fourloops at its open end. These loops form the natural binding site of the lipocalins and can be reshaped in vitro by extensive amino acid replacement, thus creating novel binding specificities. The bilin-binding protein (BBP) was employed as a model system for the preparation of a random library with 16 selectively mutagenized residues. Using bacterial phagemid display and colony screening techniques, several lipocalin variants -- termed anticalins -- have been selected from this library, exhibiting binding activity for compounds like fluorescein or digoxigenin. Anticalins possess high affinity and specificity for their prescribed ligands as well as fast binding kinetics, so that their functional properties are similar to those of antibodies. Compared with them, they exhibit however several advantages, including a smaller size, composition of a single polypeptide chain, and a simple set of four hypervariable loops that can be easily manipulated at the genetic level. Apart from haptenic compounds as targets, anticalins should also be able to recognise macromolecular antigens, provided that the random library is accordingly designed. Hence, they should not only serve as valuable reagents for bioanalytical purposes, but may also have a potential in replacing antibodies for medical therapy.
机译：在特定的生命分子和生物技术领域，识别特定分子的可溶性受体蛋白的发展日益重要，例如，从小分子化合物到细胞表面的大分子结构。在过去的一个世纪中，该应用领域主要是抗体，抗体通常是通过动物免疫产生的，但最近也可以通过蛋白质工程方法获得。所谓的“ anticalins”提供了另一种类型的配体结合蛋白，它是在脂蛋白作为支架的基础上构建的。这种蛋白质结构的核心元素是八根反平行链的＃beta＃-桶状结构，在其开放端支持Fourloops。这些环形成脂环蛋白的天然结合位点，可以通过广泛的氨基酸置换在体外重塑，从而产生新的结合特异性。联蛋白结合蛋白（BBP）被用作模型系统，用于制备具有16个选择性诱变残基的随机文库。使用细菌噬菌粒展示和菌落筛选技术，已从该文库中选择了几种脂环素变体（称为anticalins），它们对诸如荧光素或洋地黄毒苷的化合物具有结合活性。 Anticalins对它们规定的配体具有很高的亲和力和特异性，并具有快速的结合动力学，因此它们的功能特性与抗体相似。然而，与它们相比，它们具有几个优点，包括较小的尺寸，单个多肽链的组成以及一组简单的四个高变环，这些环可以在遗传水平轻松操作。除了以半抗原化合物为靶标之外，只要相应地设计了随机文库，抗病毒药也应能够识别大分子抗原。因此，它们不仅应作为生物分析用途的有价值的试剂，而且还可能具有替代医学治疗用抗体的潜力。

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