PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDES

使用放射性同位素标记用于诊断的有机化合物 核医学在文献中有很好的记录。它已经找到了 某些放射性标记化合物会定位在大脑、心脏或 在其他靶器官或组织中达到足够的水平以允许 对其进行成像。 某些药物在动物或器官中的结合部位可能是定位的 作为合成高比活度放射性标记的结果 对该结合部位具有高亲和力的类似物。假肢 基团可以连接到药物或其他受体配体上以达到此目的 对特定放射性同位素的有效和选择性的化学捕获。 开发了茶碱和其他药物的功能化同系物 通过作用于腺苷受体，我们现在正在开发假体群 对于放射性同位素，如18-F、123-I和125-I，要耦合到这些 功能化的药物分子。假体基团含有氨基或 需要共价缩合到官能化的羧基 在特定受体上给予高亲和力的结合物的药物，或 不可逆地结合标签的药物(三功能试剂)。 受体可逆性亲和标记的一般方法是 发展起来的。目标是进行一系列的化学 修改会产生一个记者组。配基识别位点 牛脑膜A1-腺苷受体活性的研究 论证了这种方法的可行性。二硫化物或酯的使用 连接，旨在通过暴露于标记的受体来切割 分别考虑了还原剂或羟胺。

The use of radioisotopes to label organic compounds for use in diagnostic nuclear medicine is well documented in the literature. It has been found that certain radiolabeled compounds ill localize in the brain, heart, or in other target organs or tissues to a sufficient level to allow for imaging thereof. Binding sites for certain drugs in an animal or organ may be localized as a result of the synthesis of high specific activity radiolabeled analogs which have high affinity for that binding site. Prosthetic groups may be attached to a drug or other receptor ligand for the purpose of efficient and selective chemical capture of a particular radioisotope. Having developed functionalized congeners of theophylline and other drugs acting at adenosine receptors, we are now developing prosthetic groups for radioisotopes such as 18-F, 123-I, and 125-I, to be coupled to these functionalized drug molecules. The prosthetic groups contain amino or carboxylic groups which are to be condensed covalently to functionalized drugs to give conjugates of high affinity at a particular receptor, or drugs that bind the label irreversibly (trifunctional reagents). A general approach for reversible affinity labeling of receptors has been developed. The objective is to carry out a series of chemical modifications resulting in a reporter group. The ligand recognition site of A1-adenosine receptors in bovine brain membranes was probed to demonstrate the feasibility of this approach. Use of disulfide or ester linkages, intended for cleavage by exposure of the labeled receptor to either reducing reagents or hydroxylamine, respectively, was considered.