TRITIUM LABELING-MECHANISMS AND METHODS

氚标记机制和方法

• 批准号: 3171385
• 负责人: CHIN-TZU PENG
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3171385
• 关键词: chemical structure function; chemical synthesis; halogenation; high performance liquid chromatography; insulin; macromolecule; microwave radiation; nuclear magnetic resonance spectroscopy; peptide chemical synthesis; radiopharmacology; radiotracer; tritium

The objective of the proposed research is to study the conditions under which tritium labeled compounds such as unsaturates, polypeptides, proteins, and biomolecules, can be obtained with high specific activity and minimum degradation. The use of energy transfer agents, catalytic surfaces and graded tritium energies to increase the selectivity of tritium labeling by active species of tritium will be studied. The short duration of exposure, mild conditions, minimum radiation degradation and high specific activity can be obtained make excitation labeling the method of choice for complex molecules and biomelecules. Adsorbed or chemisorbed tritium on supported metal catalysts will be used for tritium labeling. Adsorbed tritium is the mildest tritium exchange agent and can label compounds with hydrogen sensitive groups without causing their reduction or substitution. The method can be improved to increase the amount of tritium adsorbed or chemisorbed on the catalyst so that curie amount of tritium is available for tritation of biological molecules. The use of surfaces to complex and stabilize the peptide bond and the N- and C-terminal residues in peptide molecules to minimize degradation will be investigated and, particularly, the reactions of protected and non-protected small peptides with tritium to determine how polypeptides such as interferons and insulin can be routinely labeled with high specific activity. The dehalogenation reactions, i.e., T-for-I and T-for-Br reactions are particularly useful for introducing tritium into specific positions in a molecule in the absence of hydrogen transfer catalyst and will be investigated. Dehalogenation in the presence of metal catalyst may result in tritium exchange and is undesirable. Tritium NMR spectroscopy of some of these labeled compounds will be performed by Dr. Yang of Lawrence Berkeley Laboratory.

拟议研究的目的是研究条件下 其中氚标记的化合物如不饱和化合物、多肽、 可以获得具有高比活性和 最小的退化。 使用能量转移剂、催化表面和分级氚 提高活性物质氚标记选择性的能量 将对氚进行研究。 暴露时间短、温和 条件下，最小的辐射降解和高比活度可以 所获得的结果使激发标记成为复杂的选择方法 分子和生物分子。 将使用负载金属催化剂上吸附或化学吸附的氚 用于氚标记。 吸附氚是最温和的氚交换 剂，并且可以标记具有氢敏感基团的化合物，而无需 导致它们的减少或替代。 该方法可以改进为 增加催化剂上吸附或化学吸附的氚量 居里量的氚可用于氚生物 分子。 使用表面来复合和稳定肽键和 N- 肽分子中的 C 端残基以尽量减少降解 进行调查，特别是受保护和 未保护的小肽与氚如何测定多肽 例如干扰素和胰岛素可以常规地用高特异性标记 活动。 脱卤反应，即 T-for-I 和 T-for-Br 反应是 对于将氚引入到特定位置特别有用 分子在没有氢转移催化剂的情况下将 调查了。 在金属催化剂存在下可能会发生脱卤反应 在氚交换中，这是不希望的。 其中一些标记化合物的氚核磁共振波谱将被 由劳伦斯伯克利实验室的杨博士进行。