N-（间-[¹²⁵I]碘苯基）马来酰亚胺：一种用于抗体高产率放射性标记的试剂。

N-(m-[125I]iodophenyl)maleimide: an agent for high yield radiolabeling of antibodies.

作者信息

Khawli L A, van den Abbeele A D, Kassis A I

机构信息

Department of Radiology (Nuclear Medicine), Harvard Medical School, Shields Warren Radiation Laboratory, Boston, MA 02115.

出版信息

Int J Rad Appl Instrum B. 1992 Apr;19(3):289-95. doi: 10.1016/0883-2897(92)90113-d.

DOI:10.1016/0883-2897(92)90113-d

PMID:1629018

Abstract

In an effort to radiolabel antibodies, N-(m-[125I]iodophenyl)maleimide (m-[125I]IPM) was prepared by the demetallation of an N-[m-tri-(n-butyl)stannylphenyl]maleimide intermediate. The unlabeled intermediate was synthesized in greater than or equal to 75% yield using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline, followed by reaction with maleic anhydride and ring annulation. All products were confirmed by NMR and elemental analysis. Labeling with 125I was carried out in a biphasic mixture containing chloramine-T (radiochemical yield greater than or equal to 70%). Rabbit IgG modified with the heterobifunctional crosslinking agent N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) and bovine serum albumin were conjugated with m-[125I]IPM (yield: 40 and 80%, respectively). In addition, m-[125I]IPM was conjugated to rabbit IgG subunits (HL) in 70% yield. The in vitro stability of the radiolabeled proteins in serum showed less than 1% deiodination over 24 h.

摘要

为了对抗体进行放射性标记，通过N-[间-三（正丁基）锡烷基苯基]马来酰亚胺中间体的脱金属反应制备了N-（间-[¹²⁵I]碘苯基）马来酰亚胺（间-[¹²⁵I]IPM）。未标记的中间体通过六丁基二锡与间溴苯胺的钯催化反应，然后与马来酸酐反应并进行环化反应，以大于或等于75%的产率合成。所有产物均通过核磁共振（NMR）和元素分析进行了确认。用¹²⁵I进行标记是在含有氯胺-T的双相混合物中进行的（放射化学产率大于或等于70%）。用异双功能交联剂N-琥珀酰亚胺基-3-（2-吡啶基二硫代）丙酸酯（SPDP）修饰的兔免疫球蛋白G（IgG）和牛血清白蛋白与间-[¹²⁵I]IPM偶联（产率分别为40%和80%）。此外，间-[¹²⁵I]IPM以70%的产率与兔IgG亚基（HL）偶联。放射性标记蛋白质在血清中的体外稳定性显示，在24小时内脱碘率低于1%。