MCA: Artificial glycoconjugates that target the sweet spot

Antibodies have long prevailed as therapeutic agents, as well as probes to localize proteins in order to understand their function in the cellular environment. Despite their history, antibodies are generally expensive, fragile and not universally suitable for all protein targets. This Mid-Career Advancement (MCA) project aims to identify and characterize oligonucleotide-based ligands as alternatives to antibodies for protein targets. Despite their advantages, including longer shelf-life and animal-free generation, oligonucleotide ligands are anecdotally referred to as reagents of the future due to their relatively limited implementation in biosciences and bioengineering. Through strategic partnership with a collaborator from Emory University, this project will significantly enhance the interdisciplinary skill set and research program of the principal investigator. The research and training activities aim to leverage advantages offered by oligonucleotides to broaden their practical use as biological tools across the STEM community. The goal of this research project is to expand the chemical and structural diversity of oligonucleotide screening libraries to identify superior ligands for protein targets called kinases. In lieu of popular evolutionary-based screening approaches, the research team will employ a competition-based screening platform to identify promising ligand candidates. One or more of these candidates will be tested in vitro to ascertain its kinase-specific binding capacity. This project combines macromolecular synthetic design with biological activity assessment to uncover fundamental structure-binding relationships between oligonucleotide ligands and their kinase target. 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.