DEVELOPMENT OF SMALL-MOLECULE PROBES FOR THE BETA-AMYLOID PROTEIN OF ALZHEIMERS-DISEASE
DEVELOPMENT OF SMALL-MOLECULE PROBES FOR THE BETA-AMYLOID PROTEIN OF ALZHEIMERS-DISEASE
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DOI：
10.1016/0197-4580(94)90050-7
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发表时间：
1994-11-01
影响因子：
4.2
通讯作者：
PETTEGREW, JW
中科院分区：
文献类型：
--
作者：
KLUNK, WE;DEBNATH, ML;PETTEGREW, JW
这项研究描述了小分子探针的合成和体外测试，这些探针最终可能被证明可用作活体患者淀粉样蛋白沉积的标志物。原型试剂柯胺G（CG）是刚果红的衍生物。CG在体外与合成的β-淀粉样蛋白结合良好，氟化衍生物也是如此。其结合机制似乎与刚果红相同--通过跨越几条淀粉样蛋白肽链的双齿连接。CC比刚果红亲脂性更强，在正常小鼠中可以穿过血脑屏障，达到超过10/1的脑/血比。在10倍于分布研究中使用的剂量下，小鼠中没有急性毒性。CG似乎是β-淀粉样蛋白的相对高亲和力探针，其似乎具有低毒性并且可以穿过血脑屏障。这些特性对于开发类似于CG的体内淀粉样蛋白探针是有希望的。
This study describes the synthesis and in vitro testing of small molecule probes that may eventually prove useful as markers of amyloid deposition in living patients. The prototype agent, Chrysamine G (CG), is a derivative of Congo red. CG binds synthetic beta-amyloid well in vitro, as does a fluorinated derivative. The mechanism of binding appears to be the same as Congo red-through a bidentate attachment spanning several amyloid peptide chains. CC is much more lipophilic than Congo red and crosses the blood-brain barrier in normal mice, achieving a brain/blood ratio over 10/1. There was no acute toxicity in mice at doses 10 times those used in the distribution studies. CG appears to be a relatively high affinity probe for beta-amyloid that appears to have low toxicity and can cross the blood-brain barrier. These characteristics are promising for development of in vivo amyloid probes similar to CG.