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

该奖项全部或部分根据2021年美国救援计划法案（公法117-2）资助。 在这个项目中，由数学和物理科学理事会资助，并设在化学部，教授Arundhati Nag和她的学生在克拉克大学，伍斯特，MA将致力于设计含磷酸盐代谢物的传感器。代谢途径如糖酵解使用磷酸盐形成中间代谢物，并且含磷酸盐的代谢物的水平可以提供与人类疾病如癌症有关的重要信息。Nag实验室将专注于开发三磷酸腺苷（一种核苷磷酸代谢物）和葡萄糖-6-磷酸（一种糖磷酸代谢物）的传感器，它们属于两种不同的重要含磷酸盐代谢物。代表性不足的少数民族（URM）的学生将参与这项研究，通过夏季奖学金和指导研究与教授纳格。Nag教授还将参与克拉克大学URM学生社区的发展，她和她的学生将参加外展活动，并为地区高中举办研讨会。Nag教授将开发一种综合方法，通过同时靶向磷酸部分和与磷酸连接的核苷或糖组分来检测含磷酸盐的代谢物。结合基序将被同化到环状荧光肽或肽模拟物文库中。文库将被设计为使得它们可以在一步反应中容易地转化为线性类似物，所述线性类似物可以使用从头测序容易地测序。将筛选环状文库以选择性结合感兴趣的含磷酸盐代谢物，并且一旦测序，该奖项反映了NSF的法定使命，并通过利用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。

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.