标有[99mTc(CO) 3+的氨基酸,并被L型氨基酸载体LAT1识别出来
Yu Liu1, Jae Kyoung Pak, Paul Schmutz
1Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland.
Journal of the American Chemical Society
|December 15, 2006
概括
研究人员开发了新的金属复合体,使用氨基酸通过l型氨基酸载体 (LAT1) 积极进入细胞. 这一突破使得金属标记分子能够有针对性地被送入细胞内空间.
科学领域:
- 放射化学 放射化学是指辐射化学.
- 药用化学 医学化学
- 分子成像学分子成像学
背景情况:
- 氨基酸载体在细胞吸收中起着至关重要的作用.
- 为金属基化合物开发有针对性的输送系统是医学的持续挑战.
研究的目的:
- 为了合成新型金属复合物,用于有针对性的细胞吸收.
- 研究这些复杂物与l型氨基酸载体 (LAT1) 的相互作用.
主要方法:
- 合成与fac-[M(CO) 3+ (M = Re,99mTc) 协调的α-氨基酸结合三脚体连接体.
- 使用不同长度的基间隔器对传送器识别和吸收的评估.
- 用 [3H]-l-phenylalanine进行抑制试验 (Ki值) 和外流研究.
主要成果:
- 成功合成了含有悬浮的α-氨基酸的金属复合物.
- 吸收是由l型氨基酸载体 (LAT1) 介导的,对一个丁间隔器观察到的最佳识别.
- 最好的复合体的抑制常数 (Ki) 与人工氨基酸BCH.可比.
- 流研究证实了细胞中的活性运输,而不仅仅是结合.
结论:
- 这些新的金属复合体代表了第一个金属标记的小分子,它们被积极地内化到细胞内空间.
- 这些发现证明了LAT1的潜力,作为将金属制剂输入细胞的目标.
- 这项工作为开发向放射性药物和诊断剂开辟了新的途径.
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