MCA: Artificial glycoconjugates that target the sweet spot

MCA：针对最佳甜蜜点的人造糖复合物

• 批准号: 2321460
• 负责人: Valeria Milam
• 金额: $ 42.6万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2321460&HistoricalAwards=false
• 关键词: MCA; Artificial; glycoconjugates; target; sweet

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.

长期以来，抗体已成为治疗剂，以及探测局部蛋白质以了解其在细胞环境中的功能的探针。尽管历史悠久，但抗体通常还是昂贵，脆弱的，并且不适合所有蛋白质靶标。这个中期的进步（MCA）项目旨在识别和表征基于寡核苷酸的配体作为蛋白质靶标的抗体的替代方法。尽管它们具有优势，包括较长的保质期和无动物的产生，但由于它们在生物科学和生物工程中的实施相对有限，因此偶然被称为未来的试剂。通过与埃默里大学（Emory University）的合作者的战略伙伴关系，该项目将显着增强主要研究人员的跨学科技能和研究计划。研究和培训活动旨在利用寡核苷酸提供的优势，以扩大其在STEM社区中作为生物工具的实际用途。该研究项目的目的是扩大寡核苷酸筛选库的化学和结构多样性，以识别用于蛋白质目标的优质配体称为激酶。该研究团队将代替流行的基于进化的筛查方法，将采用基于竞赛的筛查平台来确定有希望的配体候选者。这些候选者中的一个或多个将在体外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结合在一起，以发现寡核苷酸配体之间的基本结构结合关系及其激酶目标。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力和更广泛影响的Criteria进行评估的支持，可以通过评估来获得。 。