Photon Upconversion Probes with Lanthanide Containing Biomolecules

镧系离子介导的近红外光到可见光的上转换正在迅速成为一种重要的现象，在生物科学，包括成像和医学等领域有许多应用。使用单一或不同金属离子的组合，镧系元素能够使用低功率激光器将近红外（nIR）光转换为可见光，并且在成像方面比传统光源更有希望，因为生物组织和材料在这种光学窗口中对辐射更加透明，并且该机制允许获得高分辨率的3D图像。然而，目前的上转换系统仅限于固态材料，并且是上转换荧光粉或自组装的超分子离散金属团簇，这些超分子离散金属团簇具有动力学不稳定性，只能在氘化溶剂中工作。在化学，生物学和物理学的界面，该项目将涉及制造一系列生物分子（蛋白质，酶，肽）和模拟物，这些模拟物能够协调一个或几个镧系离子彼此靠近，或近红外染料天线，以创建一类新的上转换分子，用于生物探针开发，生物传感和成像应用。该项目的具体目标是：筛选各种镧系和近红外染料系统，使用统计方法和正交保护合成方法在小聚氨基羧酸盐分子中进行上转化，以合成/设计合适的氘化和非氘化肽。结合金属特异性结合域和合适受体FRET染料的酶和蛋白质，以钙调素和蓝调素开始，利用最先进的和时间相关的实验来表征这些系统的光物理特性，以测试合成的上转化生物分子在生物传感和成像应用中的潜力

Upconversion of near infra-red light to visible light mediated by lanthanide ions is rapidly emerging as an important phenomenon with many applications in biological sciences, including imaging and medicine, amongst others. Using a single or a combination of different metal ions, lanthanides are capable of converting near infra-red (nIR) light into visible light using low powered lasers and offer much promise over conventional light sources in imaging since biological tissue and materials are much more transparent to radiation in this optical window and the mechanism allows high resolution 3D images to be obtained. However, current upconverting systems are limited to solid-state materials, and are upconverting phosphors or are self assembled supramolecular discrete metal clusters that are kinetically labile and only operate in deuterated solvents. At the interface of chemistry, biology and physics, this project will involve fabrication of a range of biomolecules (proteins, enzymes, peptides) and mimics that are capable of coordinating one or several lanthanide ions in close proximity to one another or a nIR dye antenna to create a new class of upconverting molecule that operates in water for use in biological probe development, biosensing and imaging applications.Specific aims of the project are: To screen a variety of lanthanide and nIR dye systems for upconversion in small polyaminoacrboxylate molecules using statistical methods and then orthogonal protection synthetic methodsTo synthesise/engineer suitable deuterated and non-deuterated peptides, enzymes and proteins incorporating metal specific binding domains and suitable acceptor FRET dyes beginning with Calmodulin and LanmodulinTo characterise the photophysics of these systems using state of the art and time-dependent experimentsTo test the potential of the synthesised upconverting biomolecules for biosensing and imaging applications