INORGANIC BORON AND COPPER ANTIBODY LABELS FOR BIOMEDICAL APPLICATIONS

用于生物医学应用的无机硼和铜抗体标签

• 批准号: 6204068
• 负责人: JOHN R WRIGHT
• 金额: $ 7.69万
• 依托单位: SOUTHEASTERN OKLAHOMA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204068
• 关键词: affinity labeling; antibody; boron; chemical group; chemical synthesis; copper; crosslink; diagnosis design /evaluation; electron microscopy; nuclear magnetic resonance spectroscopy; polymers; radionuclides; radiopharmacology; radiotracer; stable isotope

The ultimate objective of this project is to demonstrate the synthetic feasibility of novel antibody linked forms of inorganic isotopes, and the proposed work follows the hypothesis that antibody linked toxins and diagnostic probes have the potential for targeting neoplastic tissue with high specificity. Synthetic attempts will focus on boron compounds because the stable isotope 10B is being considered as a pharmacologic agent in boron-neutron capture therapies (BNCT), and on a special class of copper cluster compounds because the short-lived isotope 64Cu (half life 12.8h) is a positron emitter and of interest to positron emission tomography (PET), a diagnostic methodology. The proposed research is thus biomedically relevant because it will attempt to prepare novel pharmacological candidate substances according to a rational design. If the work is successful and if the larger biomedical community chooses to develop the envisioned substances into actual technologies, then the work could have an impact upon neoplastic diseases. The boron investigation will focus on colloidal dispersions of a polymer which contains the phenylboronic acid structural unit, and an established palladium catalyzed coupling reaction with aryl halides will be used in an attempt to modify the surface of this colloid to a form suitable for crosslinking with immunoglobulins. Similarly, either an established amidation reaction or a strong interaction with cationic entities (polyamines) will be the basis of an attempt to link the copper cluster compounds to immunoglobulins. Biological specificity will be tested with a readily available antigen and its corresponding antibody, e.g., BSA and anti-BSA.

本项目的最终目标是展示合成 新的抗体连接形式的无机同位素的可行性， 拟议的工作遵循这样的假设，即抗体连接毒素， 诊断探针具有靶向肿瘤组织的潜力 特异性高。 合成尝试将集中在硼化合物上 因为稳定同位素10B被认为是一种药理学 硼中子俘获疗法（BNCT）中的试剂，以及特殊类别 铜簇化合物，因为短寿命的同位素64Cu（一半 寿命12.8h）是正电子发射体并且对正电子发射感兴趣 断层扫描（PET），一种诊断方法。 拟议的研究是 因此具有生物医学相关性，因为它将尝试制备新的 药理学候选物质根据合理的设计。 如果 这项工作是成功的，如果更大的生物医学界选择 将设想的物质发展成实际的技术， 可能对肿瘤性疾病有影响。 硼的研究 将集中于聚合物的胶体分散体，其含有 苯基硼酸结构单元和已建立的钯 将尝试使用与芳基卤化物的催化偶联反应 为了将该胶体的表面改性为适于交联的形式 与免疫球蛋白。 类似地，要么是已建立的酰胺化 与阳离子实体（多胺）的反应或强相互作用将 是试图将铜簇合物与 免疫球蛋白。生物特异性将采用易于检测的 可用的抗原及其相应的抗体，例如，BSA和抗BSA。