Bioconjugation: Novel Reagents and Strategies for Cysteine and Disulfide Modification

该项目的目标概括如下：1.开发一种新型的硫醇稳定的哒二酮结构，以满足上述未得到满足的需求。2.研究新型炔烃与半胱氨酸和二硫化物的反应活性，以满足上述未满足的需求。3.随着核心化学平台的开发，研究用于半胱氨酸和二硫键修饰的新型底物在几种治疗应用中的应用。因此，该项目旨在为EPSRC的医疗保健技术主题做出促进贡献，并直接与开发未来疗法的重大挑战保持一致；特别是在开发以各种方式增强药物输送的先进技术方面。这项建议直接涉及的更广泛的研究领域是“化学生物学和生物化学”，这是EPSRC的一个关键研究领域。我们开发一种新的共轭技术来从根本上实现新的研究领域，并为最近发现的现有领域增加价值，这将进一步巩固英国在该领域的前沿地位。此外，这项研究将补充EPSRC在临床技术和生物材料领域现有的约9500万GB的投资，从而巩固英国科学在这些领域的世界领先地位。

The aims of the project are summarised as follows: 1. To develop a novel thiol stable pyridazinedione construct to address the above-mentioned unmet needs. 2. To investigate the reactivity of novel alkynes on reaction with cysteine and disulfides to also address the above-mentioned unmet needs. 3. To investigate the use of novel substrates for cysteine and disulfide modification in several therapeutic applications following the development of the core chemistry platform. This project thus aims to make a facilitating contribution in the EPSRC theme of Healthcare Technologies and is directly aligned with the grand challenge of Developing Future Therapies; especially in developing 'advanced technologies to enhance drug delivery' in various manners. The broader research area that this proposal directly links with is 'Chemical Biology and Biological Chemistry'; a key EPSRC research area. Our approach to developing a novel conjugation technology to enable fundamentally new areas of research, and add value to existing ones that have recently been unearthed, would further consolidate the UK's place at the forefront of this field. Moreover, this research will complement the existing ca. £95 million investment the EPSRC has in the areas of clinical technologies and biomaterials, thus consolidating UK science as world-leaders in these arenas.