RUI: Targeting the Terminus for Site-Specific Recognition and Labeling of Proteins

RUI：针对蛋白质位点特异性识别和标记的终点

• 批准号: 1309978
• 负责人: Adam Urbach
• 金额: $ 33万
• 依托单位: Trinity University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309978&HistoricalAwards=false
• 关键词: RUI; Targeting; Terminus; Site; Specific

In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Adam Urbach of Trinity University explores the hypothesis that the terminus of a polypeptide chain has unique structural and conformational properties that may provide a general approach to protein recognition that is specific to a single site and is predictable both from the sequence of amino acids and from the receptor's ability to recognize short peptides of the same sequence. The project has three complementary aims. The first aim focuses on the discovery and characterization of new motifs for the recognition of peptide termini by synthetic receptors. The second part asks whether these receptors can recognize proteins containing the same terminal sequences. The third part involves the application of the recognition work to the labeling, capture, and release of proteins using conjugates of the synthetic receptors to bring functionality to the terminus of the proteins targeted in these studies. In addition to the societal benefits of being able to identify, isolate, and label specific proteins, the broader impacts involve intense training of undergraduate students in the research laboratory and a plan for the training of postdoctoral scholars that addresses crucial aspects of professional development in scholarship, teaching, and service in order to best prepare them to begin a career at a primarily undergraduate institution.The ability to distinguish between the numerous proteins in living systems is crucial to biological and biotechnological processes, but currently only antibodies can do this reliably and antibody-based technology can be very costly. This research aims to address this problem by developing new methods for interacting with proteins using synthetic receptors, which can be much less expensive and easier to modify. The focus of this project is to explore the recently developed concept that the very end of a protein chain (the terminus) is an ideal site for interacting with a receptor because the tail, like the end of a ball of string, can easily unravel. If successful, this research would establish a general method for predictably interacting with proteins, and it would form the foundation for developing tools that substantially improve our understanding of protein function in living systems.

在化学系高分子、超分子和纳米化学项目资助的这个项目中，三一大学（Trinity University）的Adam Urbach探索了这样一种假设：多肽链末端具有独特的结构和构象特性，这可能提供一种蛋白质识别的通用方法，该方法对单个位点具有特异性，并且可以从氨基酸序列和受体识别能力来预测相同序列的短肽。该项目有三个相辅相成的目标。第一个目标集中在发现和表征新的图案识别肽末端的合成受体。第二部分探讨这些受体是否能够识别含有相同末端序列的蛋白质。第三部分涉及识别工作的应用，以标记，捕获和释放的蛋白质，使用合成受体的缀合物，使功能的蛋白质在这些研究中的目标的末端。除了能够识别，分离和标记特定蛋白质的社会效益外，更广泛的影响还包括在研究实验室对本科生进行密集培训，以及培养博士后学者的计划，该计划涉及学术，教学，区分生命系统中众多蛋白质的能力对生物学和生物学的发展至关重要，生物技术过程，但目前只有抗体可以做到这一点可靠和抗体为基础的技术可能是非常昂贵的。这项研究旨在通过开发使用合成受体与蛋白质相互作用的新方法来解决这个问题，这种方法可以更便宜，更容易修改。该项目的重点是探索最近发展的概念，即蛋白质链的末端（末端）是与受体相互作用的理想场所，因为尾巴就像一个线团的末端，可以很容易地解开。如果成功，这项研究将建立一种可预测的与蛋白质相互作用的通用方法，并将为开发工具奠定基础，从而大大提高我们对生命系统中蛋白质功能的理解。