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

Clark University, Worcester MA

Investigators

Abstract

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.