Development of a library of regulated Actibodies

描述(申请人提供)：识别蛋白，如抗体，在医学和生物技术中有许多应用。这些应用中的许多都将受益于控制或激活识别蛋白与目标结合的能力。这项提议寻求开发和测试一个可激活的抗体激发的识别蛋白或活性体库。具体地说，我们首先的目标是将多样性引入到一种受调控的蛋白质中，并开发一种适合该蛋白质的新的展示系统和伴随的筛选技术。然后，我们将确定以这种方式选择的单个变体识别目标分子的能力。在我们的第二个目标中，我们将确定这个文库的成员是否真的是主动体，可以被激活来结合靶标。这项工作将帮助我们理解一种新发现的变构调节类型，并确定它是否有助于制造受调节的识别蛋白。由此产生的作用体技术应该有助于一系列生物医学技术，包括靶向药物输送、分子成像、体外诊断和分离技术。具体地说，激活结合的能力应该增强在所有应用中仅具体识别正确靶的能力，并且还将允许在体外应用中温和地恢复靶。

DESCRIPTION (provided by applicant): Recognition proteins, such as antibodies, have many applications in medicine and biotechnology. Many of these applications would benefit from the ability to control, or activate, when the recognition protein binds to the target. This proposal seeks to develop and test a library of activatable antibody-inspired recognition proteins, or actibodies. Specifically, we first aim to introduce diversity into a regulated protein and develop a new display system and accompanying screening technology that is appropriate for this protein. We will then determine how well individual variants selected in this fashion can recognize the target molecules. In our second aim, we will determine whether members of this library are indeed actibodies, that can be activated to bind the target. This work will help us understand a newly discovered type of allosteric regulation, and determine whether it is useful for making regulated recognition proteins. The resulting actibody technology should contribute to a range of biomedical technologies, including targeted drug delivery, molecular imaging, in vitro diagnostics, and separation technologies. In particular, the ability to activate binding should enhance the ability to specifically identify only the correct target in all applications, and would also allow for gentle recovery of the target in the in vitro applications.