Radiosynthesis of new [90Y]-DOTA-based maleimide reagents suitable for the prelabeling of thiol-bearing L-oligonucleotides and peptides.
Radiosynthesis of new [90Y]-DOTA-based maleimide reagents suitable for the prelabeling of thiol-bearing L-oligonucleotides and peptides.
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DOI：
10.1021/bc900095k
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发表时间：
2009-06
影响因子：
4.7
通讯作者：
Joern Schlesinger;Cindy R. Fischer;Inge Koezle;S. Vonhoff;S. Klußmann;R. Bergmann;H. Pietzsch;J. Steinbach
中科院分区：
文献类型：
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作者：
Joern Schlesinger;Cindy R. Fischer;Inge Koezle;S. Vonhoff;S. Klußmann;R. Bergmann;H. Pietzsch;J. Steinbach
我们描述了两种新的基于[(90)Y]- dota的马来酰亚胺试剂的放射性合成，适用于l- rna和含硫醇连接体修饰的肽的轻度放射性标记。以固相萃取（SPE）为纯化方法，优化了含（90）Y的含（90）Y配合物[{（2S)-2-[4-（2,5-二氧基-2,5-二氢- 1h -吡咯-1-基）苄基]-1,4,7,10-四氮杂环十二烷-1,4,7,10-四氮杂环十二烷-1,4,7 -二氢- 1h -吡咯-1-基）苄基][(90)Y] ytrate (1-)（[(90)Y]4）和[{(2S)-2-(4)-{[4-（2,5-二氧基-2,5-二氢- 1h -吡咯-1-基）丁基]氨基苄基]-1,4,7,10-四氮杂环十二烷-1,4,7,10-四氢基]四氮杂环十二烷][(90)Y] ytrate (1-)（[(90)Y]4）的合成工艺。通过预先标记谷胱甘肽（GSH）和巯基修饰的12mer L-RNA作为模型物质，初步评估了这两种马来酰亚胺试剂的应用和反应性。与n -芳基马来酰亚胺配合物[(90)Y]3相比，n -烷基马来酰亚胺配合物[(90)Y]4在pH为>或= 7时的水解稳定性有所提高。在室温下，分别用0.1和1微克谷胱甘肽预标记磷酸盐缓冲液（pH为7.2），发现[(90)Y]3的反应性略高。在非常高的放射化学产率方面，用[(90)Y]YCl(3)直接标记DOTA-L-RNA偶联物比用[(90)Y]4预先标记巯基修饰的12mer L-RNA衍生物更合适。
We describe the radiosynthesis of two new [(90)Y]-DOTA-based maleimide reagents, suitable for the mild radiolabeling of L-RNAs and peptides modified with thiol-bearing linkers. The synthesis procedure of both maleimide-bearing (90)Y complexes, [{(2S)-2-[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl}tetraacetato][(90)Y]yttrate(1-)([(90)Y]3) and [{(2S)-2-(4-{[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoyl]amino}benzyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetrayl]tetraacetato}[(90)Y]yttrate(1-)([(90)Y]4), was optimized in terms of an easy purification method via solid-phase extraction (SPE). Application as well as reactivity of both maleimide reagents were initially evaluated by the prelabeling of glutathione (GSH) and a thiol-modified 12mer L-RNA as model substances. In comparison to the N-aryl maleimide-bearing complex [(90)Y]3, N-alkyl maleimide-bearing complex [(90)Y]4 showed an increased hydrolytic stability at pH > or = 7. A slightly higher reactivity was found for [(90)Y]3 by prelabeling of 0.1 and 1 microg glutathione, respectively, in phosphate buffer (pH 7.2) at room temperature. In terms of very high radiochemical yields, the direct radiolabeling of DOTA-L-RNA conjugate with [(90)Y]YCl(3) proved to be more suitable than the prelabeling of the thiol-modified 12mer L-RNA derivative with [(90)Y]4.