NSF LEAPS-MPS: Macrocyclic Peptidomimetic Scaffolds for Sensing of Phosphate-containing Metabolites

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。这个项目由数学和物理科学委员会资助，设在化学系，马萨诸塞州伍斯特市克拉克大学的Arundhati Nag教授和她的学生将致力于设计含磷代谢物的传感器。糖酵解等代谢途径使用磷酸盐形成中间代谢物，而含有磷酸盐的代谢物的水平可以提供与癌症等人类疾病有关的重要信息。NAG实验室将专注于开发三磷酸腺苷和葡萄糖-6-磷酸的传感器，三磷酸腺苷是一种核苷磷酸盐代谢物，葡萄糖-6-磷酸是一种糖磷酸盐代谢物，属于两类不同的含磷代谢物。未被充分代表的少数族裔(URM)学生将参与这项研究，通过暑期奖学金和与NAG教授的指导研究。Nag教授还将参与克拉克大学的URM学生社区的开发，她和她的学生将参加外展活动，并为地区高中开发工作坊。Nag教授将开发一种全面的方法，通过同时针对磷酸盐部分和附着在磷酸盐上的核苷或糖成分来感应含磷的代谢物。结合基序将被同化成环状荧光多肽或模拟多肽文库。文库的设计将使得它们可以很容易地在一步反应中转换成线性类似物，从而可以很容易地使用从头测序进行测序。将对环状文库进行筛选，以选择性地结合感兴趣的含磷代谢物，并对筛选后的点击进行研究，以帮助了解传感器与代谢物的哪些相互作用对于选择性检测代谢物至关重要。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Arundhati Nag and her students at Clark University, Worcester, MA will work on designing sensors for phosphate-containing metabolites. Metabolic pathways such as glycolysis use phosphate to form intermediate metabolites, and the levels of the phosphate containing metabolites can provide important information implicated in human diseases such as cancer. The Nag lab will focus on developing sensors for adenosine triphosphate, a nucleoside phosphate metabolite, and for glucose-6-phosphate, a sugar phosphate metabolite, which belong to two different important classes of phosphate-containing metabolites. Underrepresented minority (URM) students will be involved in this research, through summer fellowship and directed studies with Professor Nag. Prof. Nag will also be involved in developing a community of URM students at Clark University thorough mingles, and she and her students will participate in outreach activities and develop workshops for regional high schools.Professor Nag will develop a comprehensive approach for sensing phosphate-containing metabolites by targeting simultaneously both the phosphate moiety and the nucleoside or sugar component attached to the phosphate. The binding motifs will be assimilated into cyclic fluorescent peptidic or peptidomimetic libraries. The libraries will be designed such that they can be easily converted in a one-step reaction to linear analogs that can be readily sequenced using de novo sequencing. The cyclic libraries will be screened for selectively binding the phosphate-containing metabolite of interest, and the hits from the screen, once sequenced, will be studied to help understand which interactions of the sensor with a metabolite are critical for selective detection of metabolites.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.