Chemical synthesis and biological evaluation of conotoxin peptides

芋螺毒素肽的化学合成及生物学评价

• 批准号: 2607113
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2607113
• 关键词: Chemical; synthesis; biological; evaluation; conotoxin

Peptides derived from natural sources are useful lead compounds to develop therapeutics. The structural diversity of naturally occurring peptides covers a large section of chemical space that sits between more traditional small molecules (<500 daltons) and biologics (typically proteins). Peptides typically have excellent selectivity and binding affinity for their targets. However, they have physicochemical issues that limit their development as drugs. These include poor blood plasma stability due to proteolytic degradation and limited bioavailability because they are unable to cross membrane structures, due to their inherent polarity. The Jamieson Group's ongoing research program (Chem. Sci., 2019, 10, 1671) is focused on the development of new peptidomimetic chemistries that can be used to overcome the physicochemical limitations of peptides and facilitate peptide drug discovery. This is achieved by chemically modifying the peptide structure; removing the vulnerable functionality and introducing chemical mimic structures to retain the overall 3-dimensional structure of the peptide. Using these synthetic molecules we are investigating the nature of molecular recognition between conotoxins and the nicotinic acetylcholine receptor (nAChR).

衍生自天然来源的肽是用于开发治疗剂的有用的先导化合物。天然存在的肽的结构多样性涵盖了位于更传统的小分子（<500道尔顿）和生物制剂（通常是蛋白质）之间的大部分化学空间。肽通常对其靶标具有优异的选择性和结合亲和力。然而，它们具有物理化学问题，限制了它们作为药物的发展。这些包括由于蛋白水解降解导致的血浆稳定性差和由于它们固有的极性而不能穿过膜结构导致的有限的生物利用度。Jamieson集团正在进行的研究计划（Chem. Sci.，2019，10，1671）专注于开发新的拟肽化学物质，可用于克服肽的物理化学限制并促进肽药物的发现。这是通过化学修饰肽结构来实现的;去除脆弱的功能并引入化学模拟结构以保留肽的整体三维结构。使用这些合成的分子，我们正在研究芋螺毒素和烟碱乙酰胆碱受体（nAChR）之间的分子识别的性质。