Baidoo K E, Lever S Z
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205-2179.
Bioconjug Chem. 1990 Mar-Apr;1(2):132-7. doi: 10.1021/bc00002a007.
The synthesis of a bifunctional chelating agent (BCA), 1, based on the diaminedithiol (DADT) ligand system, is described. The six-step synthetic sequence has been accomplished in 16% overall yield, affording 1, which contains a thiolactone as a reactive moiety, which permits direct coupling to nucleophiles without the formation of byproducts. The reactivity of 1 toward benzylamine and subsequent labeling of the ligand with technetium-99m has been evaluated as a model for preparation of various bioconjugates. Both coupling and exchange labeling occur in high yield under mild conditions, and competition reactions with diethylenetriaminepentaacetic acid (DTPA) indicate the superior stability of the technetium-99m-DADT complex. Preparation of BCA 1 thus provides a new avenue into technetium-labeled radiopharmaceuticals.
本文描述了一种基于二胺二硫醇（DADT）配体体系的双功能螯合剂（BCA）1的合成。六步合成序列的总产率为16%，得到了1，它含有一个硫代内酯作为反应性部分，这使得它能够直接与亲核试剂偶联而不形成副产物。作为制备各种生物缀合物的模型，评估了1对苄胺的反应性以及随后用99m锝对配体进行标记的情况。在温和条件下，偶联和交换标记均以高产率发生，与二亚乙基三胺五乙酸（DTPA）的竞争反应表明99m锝-DADT配合物具有更高的稳定性。因此，BCA 1的制备为99m锝标记的放射性药物开辟了一条新途径。
