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

在这个由化学部大分子、超分子和纳米化学项目资助的项目中，三一大学的Adam Urbach探索了一个假设，即多肽链的末端具有独特的结构和构象特性，可以提供一种通用的方法来识别特定于单个位点的蛋白质，并且可以通过氨基酸序列和受体识别相同序列的短肽的能力来预测。该项目有三个互补的目标。第一个目标是发现和鉴定合成受体识别肽末端的新基序。第二部分询问这些受体是否可以识别含有相同末端序列的蛋白质。第三部分涉及识别工作在标记、捕获和释放蛋白质方面的应用，使用合成受体的偶联物将功能带到这些研究中所针对的蛋白质的末端。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对研究实验室本科生的强化训练，以及对博士后学者的培训计划，该计划涉及奖学金、教学和服务等专业发展的关键方面，以便为他们在主要的本科机构开始职业生涯做好最好的准备。区分生命系统中众多蛋白质的能力对生物和生物技术过程至关重要，但目前只有抗体可以可靠地做到这一点，而基于抗体的技术可能非常昂贵。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，这种方法可以便宜得多，也更容易修改。这个项目的重点是探索最近发展的概念，即蛋白质链的最末端（终端）是与受体相互作用的理想地点，因为尾巴，就像绳子球的末端，很容易解开。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，这些工具将大大提高我们对生命系统中蛋白质功能的理解。

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.