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: 6107001
• 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: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107001
• 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.

该项目的最终目标是展示合成 新型抗体连接形式的无机同位素的可行性，以及 拟议的工作遵循抗体与毒素相关的假设 诊断探针具有靶向肿瘤组织的潜力 高特异性。 合成尝试将集中于硼化合物 因为稳定同位素 10B 被认为是一种药物 硼中子俘获疗法 (BNCT) 和特殊类别的药剂 铜簇化合物的存在是因为短寿命同位素 64Cu（半 life 12.8h) 是正电子发射体，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，因为它将尝试准备新颖的 根据合理设计的药理候选物质。 如果 这项工作是成功的，如果更大的生物医学界选择 将设想的物质开发成实际的技术，然后开展工作 可能对肿瘤疾病产生影响。 硼调查 将重点关注包含以下成分的聚合物的胶体分散体 苯基硼酸结构单元，以及已建立的钯 将尝试使用与芳基卤化物的催化偶联反应 将该胶体的表面改性为适合交联的形式 与免疫球蛋白。 同样，既定的酰胺化 与阳离子实体（多胺）的反应或强相互作用将 是尝试将铜簇化合物连接到的基础 免疫球蛋白。生物特异性将通过简单的测试 可用的抗原及其相应的抗体，例如BSA和抗BSA。