Photon Upconversion Probes with Lanthanide Containing Biomolecules

由镧系元素离子介导的近红外光到可见光的上转换正迅速成为一种重要现象，在生物科学中具有许多应用，包括成像和医学等。使用单个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）光转换成可见光，并且在成像中提供优于常规光源的前景，因为生物组织和材料对该光学窗口中的辐射更加透明，并且该机制允许获得高分辨率3D图像。然而，目前的上转换系统限于固态材料，并且是上转换磷光体或者是动力学不稳定的并且仅在氘代溶剂中操作的自组装超分子离散金属簇。在化学，生物学和物理学的界面上，该项目将涉及一系列生物分子的制造（蛋白质、酶、肽）和模拟物，其能够将一种或几种镧系元素离子彼此紧密接近地配位或与NIR染料天线配位，以产生一类新的上转换分子，其在水中操作以用于生物探针开发，该项目的具体目标是：为了使用统计方法和正交保护合成方法筛选各种镧系元素和nIR染料系统用于小聚氨基丙烯酸酯分子中的上转换，为了合成/工程化合适的氘代和非氘代肽，酶和蛋白质掺入金属特异性结合结构域和合适的受体FRET染料，从钙调素和兰调素开始使用现有技术和时间依赖性实验来验证这些系统的生物物理学，以测试合成的上转换生物分子用于生物传感和成像应用的潜力

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