ANTIBODY LIKE BINDING POCKET ON A ROBUST FRAMEWORK

该提案描述了一种结合蛋白的设计， 重要的抗体结合位点特征与蛋白质框架 这是强大的。抗体通常具有相当低的稳定性， 轻链和重链可变区之间的关联通常较弱， 这些结构域一起形成抗原结合位点。这 稳定性问题在重组抗体中更为突出， 通过删除恒定的 区域域。尽管它们的分子简化了， 在结构上，重组抗体通常非常低效地折叠， 细菌，可能是由于它们的二聚体结构和真核生物 起源所提出的结合蛋白设计利用了一个框架， 基于来自嗜热酶的单一蛋白质结构域， 原核生物起源这不仅有望赋予拟议的 结合蛋白具有高度的稳定性，但它也应该 促进在大肠杆菌中的有效表达。 所提出的结合蛋白设计将实现这些增强的 结构特征而不损害结合位点特征。的 互补决定区域状环的排列和数目 类似于抗体，因此这些结合蛋白 预期通过广泛的免疫反应获得高亲和力和特异性。 组合位点几何形状的多样性。 拟定商业应用： 抗体结合特异性的多样性使得它们可用于 各种各样的应用。提出的结合蛋白是 也期望有这个强大的财产，但与增加 在大肠杆菌中高效表达的好处，高稳定性，小 规模和潜在的亲和力比这更高 通常在抗体中可见。

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.