MCA: Artificial glycoconjugates that target the sweet spot

长期以来，抗体一直被用作治疗剂，以及定位蛋白质的探针，以了解它们在细胞环境中的功能。尽管有其历史，抗体通常是昂贵的，脆弱的，并且并不是所有的蛋白质靶标都适用。这一职业生涯中期推进(MCA)项目旨在确定和表征基于寡核苷酸的配体作为蛋白质靶标抗体的替代品。尽管寡核苷酸配体具有货架期更长、无动物繁殖等优点，但由于其在生物科学和生物工程中的应用相对有限，因此被坊间称为未来的试剂。通过与埃默里大学的合作者建立战略合作伙伴关系，该项目将显著提高首席研究员的跨学科技能和研究计划。研究和培训活动的目的是利用寡核苷酸提供的优势，在STEM社区扩大其作为生物工具的实际用途。本研究项目的目标是扩大寡核苷酸筛选文库的化学和结构多样性，以确定被称为蛋白靶标的优质配体。代替流行的基于进化的筛选方法，研究团队将采用基于竞争的筛选平台来确定有前途的配体候选。这些候选中的一个或多个将在体外进行测试，以确定其激酶特异性结合能力。该项目将大分子合成设计与生物活性评估相结合，以揭示寡核苷酸配体与其激酶靶标之间的基本结构结合关系。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。

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.