Flexible Peptide Decorated Polyaminocarboxylate Ligands for Selective Extraction of Radiotherapeutic Metals for Targeted Alpha Cancer Therapy

用于选择性提取放射治疗金属以用于靶向α癌症治疗的柔性肽修饰的聚氨基羧酸盐配体

• 批准号: 2786514
• 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: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2786514
• 关键词: Flexible; Peptide; Decorated; Polyaminocarboxylate; Ligands

Nuclear fission produces radioactive isotopes with decay products encompassing a large proportion of the Periodic Table. Many of these isotopes are considered as waste and are currently disposed of following separation. However, a number of medically useful therapeutic radioisotopes are contained within this waste stream and remain an untapped resource; specifically alpha therapeutic agents such as Ac-225 and Pb-212 (originating from uranium and thorium) which may be used for cancer treatment. Reactor produced radionuclides require rapid and selective separation in a few simple steps before they can undergo bioconjugation to a suitable targeting vector to make them viable as cancer therapeutics. However, the coordination chemistry of these radionuclides differs and achieving direct selective extraction remains challenging. We have recently developed a one pot procedure to selectively extract the long-lived minor actinides from the lanthanides using flexible multidentate polyaminocarboxylate extractants functionalised with amino acids. These are resistant to gamma radiation, operate over a wide pH range,exhibit rapid complexation kinetics; they are easily modified to alter the selectivity for a given metal based on ionic radii and coordination donor preferences.

核裂变会产生放射性同位素，其中腐烂产物包括大部分元素周期表。这些同位素中的许多被认为是废物，目前正在处理以下分离。但是，在此废物流中包含许多医学上有用的放射性病，并且仍然是未开发的资源。特别是AC-225和PB-212（起源于铀和or）等α治疗剂，可用于癌症治疗。反应堆产生的放射性核素需要以几个简单的步骤进行快速和选择性的分离，然后才能将生物缀合与合适的靶向载体进行生物缀合，以使其成为癌症疗法。然而，这些放射性核素的配位化学反应与直接选择性提取的不同，仍然具有挑战性。我们最近开发了一种一种盆栽程序，可以使用柔性多齿聚氨基羧酸盐提取物与氨基酸官能化，从而选择性地从灯笼中选择长寿命的小肌动剂。这些对伽马辐射具有抗性，在宽的pH范围内运行，表现出快速的络合动力学。它们很容易修改以根据离子半径和协调供体的偏好改变给定金属的选择性。