ANTIBODY LIKE BINDING POCKET ON A ROBUST FRAMEWORK

这项提案描述了一种结合蛋白质的设计，它融合了 结合位点特征和蛋白质骨架的重要抗体 这很有说服力。抗体的稳定性一般较低，这是由于 与轻链和重链变量之间的关联通常很弱 一起形成抗原结合部位的结构域。这 稳定性问题在重组抗体中被突出，这些抗体是 通过删除常量在原核生物中进行生产的工程 区域域。尽管他们的分子被简化了 架构，重组抗体在体内的折叠效率通常非常低 细菌，可能是由于它们的二聚体结构和真核生物 起源。建议的结合蛋白设计利用了一个框架 基于来自嗜热酶的单个蛋白结构域 起源于原核生物。预计这不仅将赋予拟议的 结合蛋白质具有高度的稳定性，但它也应该 促进在大肠杆菌中的高效表达。 建议的结合蛋白设计将实现这些增强 在不影响结合位点特征的情况下具有结构特征。这个 互补判定类区域环的排列和数目 与抗体相似，因此这些结合蛋白是 期望通过广泛的应用实现高亲和力和特异性 结合部位几何形状的多样性。 建议的商业应用： 抗体结合特性的多样性使它们在 种类繁多的应用。建议的结合蛋白是 也希望拥有这个强大的属性，但添加了 在大肠杆菌中高效表达的优点，稳定性高，体积小 大小和潜在的亲和力高于这一点 通常见于抗体中。

This proposal describes a binding protein design that merges important antibody combining site features with a protein framework that is robust. Antibodies generally have rather low stabilities due to the often weak association of the light and heavy chain variable domains that together, form the antigen combining site. This stability problem is accentuated in recombinant antibodies, which are engineered for production in prokaryotes by deletion of constant region domains. Despite simplification of their molecular architecture, recombinant antibodies often fold very inefficiently in bacteria, presumably due to their dimeric structure and eukaryotic origin. The proposed binding protein design utilizes a framework based on a single protein domain from a thermophilic enzyme of prokaryotic origin. Not only is this expected to endow the proposed binding proteins with a high degree of stability, but it should also facilitate efficient expression in E.coli. The proposed binding protein design will achieve these enhanced structural features without compromising binding site character. The arrangement and number of complementary determining region-like loops is similar to that of antibodies and thus these binding proteins are expected to achieve high affinity and specificity through a wide diversity of combining site geometries. PROPOSED COMMERCIAL APPLICATION: The diversity of antibody binding specificities makes them useful in an immense variety of applications. The proposed binding-proteins are also expected to have this powerful property, but with the added benefits of efficient expression in E.coli, high stability, small size and a potential for affinities that are higher than that normally seen in antibodies.