Bioconjugation: Novel Reagents and Strategies for Cysteine and Disulfide Modification

该项目的目标总结如下：1。开发新型硫醇稳定的哒嗪二酮构建体以解决上述未满足的需求。2.研究新型炔与半胱氨酸和二硫化物反应的反应性，以解决上述未满足的需求。3.在核心化学平台开发后，研究新型半胱氨酸和二硫键修饰底物在几种治疗应用中的用途。因此，该项目旨在为EPSRC的医疗保健技术主题做出促进性贡献，并直接与开发未来疗法的巨大挑战保持一致;特别是以各种方式开发“先进技术以增强药物输送”。更广泛的研究领域，这一建议直接联系是“化学生物学和生物化学”;一个关键的EPSRC研究领域。我们开发新型共轭技术的方法，使新的研究领域从根本上成为可能，并为最近发现的现有研究领域增加价值，这将进一步巩固英国在这一领域的前沿地位。此外，这项研究将补充现有的案例。EPSRC在临床技术和生物材料领域投资9500万英镑，从而巩固了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.