Peptide Decorated Multinuclear Lanthanide Architectures for Dual Imaging and Delivery Applications

用于双成像和传输应用的肽修饰多核稀土架构

• 批准号: 2105099
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2105099
• 关键词: Peptide; Decorated; Multinuclear; Lanthanide; Architectures

Short peptides, comprising of 8-40 amino acids, are increasingly being used to deliver payloads through cell membranes and to specific subcellular compartments (ACSNano, 2014, 8, 1972). This project will utilize known conjugation strategies (Analyst, 2010, 135, 42) to append peptides of defined sequences to luminescent, self-assembling Ln3+ architectures, thus providing a strategy to simultaneously control and visualize cellular localization of a delivery vehicle, and hence payload.The PhD student assigned to this project will synthesize and characterize a selection of lanthanide and mixed lanthanide-transition metal complexes; the coordination motifs that endow the best aqueous stability and imaging properties (i.e. quantum yield and lifetime) will then be incorporated into metal organic constructs functionalized with pendant peptide sequences known to localize to specific intracellular organelles. Cellular uptake and localization will be evaluated, to ensure the cellular localization properties of the peptide are retained once conjugated to the lanthanide complex. The final stage of this project will then be to tailor the capsules for specific guest molecules with known pharmaceutical activity. Objectives1) Develop supramolecular chemistry of lanthanides to enable construction of water-soluble architectures with internal void pockets. 2) Evaluate spectroscopic properties of constructs to identify the best systems for lanthanide imaging.3) Develop protocol for appending peptides to supramolecular architectures (transition metal and lanthanide constructs), enabling cell penetration and organelle targeting.4) Evaluate cellular uptake and imaging properties of architectures, in the presence/absence of a guest.Currently small lanthanide based architectures that are water-soluble are known, however these lack the capacity to carry a guest molecule. Larger lanthanide based structures that can accommodate guest molecules have found application as novel sensors, but these structures are insoluble or unstable in aqueous environments. This research will identify structural motifs that support both aqueous solubility and guest incorporation with an aim to develop novel drug delivery vehicles with inherent luminescence enabling them to be tracked in cells. The student will receive interdisciplinary training as they synthesize and characterize novel organic ligands and metal-organic complexes, perform extensive spectroscopic studies on the lanthanide complexes and analyze the cellular uptake of the complexes.

由8-40个氨基酸组成的短肽越来越多地用于通过细胞膜和特定的亚细胞室传递有效载荷（Acsnano，2014，8，1972）。该项目将利用已知的共轭策略（Analyst，2010，135，42）将定义序列的肽添加到发光，自组装的LN3+体系结构中，从而提供了一种策略，从而提供了一种策略，以同时控制和可视化交付工具的蜂窝定位，从而提供有效负载的蜂窝定位分配给该项目的博士生将综合并表征选择灯笼和混合灯笼型转变金属络合物的选择；然后，将赋予最佳水性稳定性和成像特性的配位基序（即量子产率和寿命），然后将其纳入具有吊坠肽序列功能化的金属有机构建体中，已知，已知的吊体肽序列已知，该构造已知，该构造已知，该构造将其定位于特定的细胞内细胞器。将评估细胞摄取和定位，以确保将肽的细胞定位特性保留到灯笼中的复合物中。然后，该项目的最后阶段将是为具有已知药物活动的特定客体分子调整胶囊。目标1）开发灯笼的超分子化学，以便能够用内部空隙的水溶液构建水溶性建筑。 2）评估构建体的光谱特性，以识别灯笼成像的最佳系统。3）开发用于将肽附加到超分子体系结构（过渡金属和灯笼构建体）的方案在存在/不存在客人的情况下，建筑物尚不知道水溶性的小型基于灯笼的建筑，但是这些结构缺乏携带客人分子的能力。可以容纳客人分子的较大的基于灯笼的结构已发现作为新型传感器的应用，但是这些结构在水性环境中是不溶性或不稳定的。这项研究将确定支持水溶性和客人合并的结构基序，以开发具有固有发光的新型药物递送车辆，从而可以在细胞中跟踪它们。该学生将在合成并表征新颖的有机配体和金属有机配合物的情况下接受跨学科训练，对兰烷化复合物进行广泛的光谱研究，并分析复合物的细胞摄取。