Development of programmable nanomachines towards the enzymatic synthesis of peptide oligonucleotide conjugates

开发用于肽寡核苷酸缀合物酶促合成的可编程纳米机器

• 批准号: EP/X019624/1
• 负责人: Purba Mukherjee
• 金额: $ 189万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX019624%2F1
• 关键词: Development; programmable; nanomachines; towards; enzymatic

This fellowship will be used to establish a multidisciplinary team working at the interface of chemistry, biology and protein engineering at the University of York, UK. The overarching goal of my group's research will be to develop novel approaches for biopolymer synthesis, design and discovery. In the process, we want to unravel the mechanisms that control and modulate the behavior of enzymes and proteins. The methodologies developed and insights gained through this proposal will inform the synthesis strategies for a new generation of therapeutics and biomaterials. Chemical synthesis remains the mainstay for the production of drugs, including the modern, next generation biologics composed of peptides, proteins, DNA, RNA, carbohydrates and their conjugates. Biomolecular conjugates have also found use as nanomaterials, drug delivery vehicles and components of biocomputers. Traditional chemical methods of synthesis require harsh conditions such as high temperature, non-aqueous solvents and non-physiological pH - parameters that are often incompatible with the manufacture of biomolecules. It is therefore imperative that alternative, sustainable strategies are explored. Enzymes present a biocompatible mode of synthesis that is starting to be exploited for the manufacture of biomolecular drugs. In this proposal, my research group will focus on adapting natural enzymes to perform the synthesis of a commonly used hybrid biomolecule - peptide-oligonucleotide conjugate. The knowledge gained will be used to further expand the existing repertoire of biologics and biomaterials.

该奖学金将用于建立一个在英国约克大学化学，生物学和蛋白质工程界面工作的多学科团队。我小组研究的总体目标是开发新的生物聚合物合成，设计和发现的方法。在此过程中，我们希望阐明控制和调节酶和蛋白质行为的机制。通过本提案获得的方法和见解将为新一代治疗和生物材料的综合策略提供信息。化学合成仍然是药物生产的主要支柱，包括由肽，蛋白质，DNA，RNA，碳水化合物及其缀合物组成的现代下一代生物制剂。生物分子缀合物还发现用作生物计算机的纳米材料，药物输送车和成分。传统的合成化学方法需要恶劣的条件，例如高温，非水溶剂和非生理pH-参数，这些参数通常与生物分子的生产不相容。因此，必须探索替代性的可持续策略。酶提出了一种生物相容性的合成模式，该模式开始被利用以生产生物分子药物。在该提案中，我的研究小组将着重于调整天然酶以执行常用的杂化生物分子 - 肽 - 寡核苷酸共轭物的合成。获得的知识将用于进一步扩大现有的生物制剂和生物材料曲目。