Laboratoire de Chimie Organique 2, INSERM U648, Universite Paris-Descartes, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
Bioconjug Chem. 2010 Feb 17;21(2):279-88. doi: 10.1021/bc900314n.
The synthesis of affinity matrices for 6-aminophenanthridine (6AP) and 2,6-dichlorobenzylidenaminoguanidine (Guanabenz, GA), two unrelated prion inhibitors, is described. In both cases, the same simple spacer, epsilon-aminocaproylaminopentanol, was introduced by a Mitsunobu reaction and the choice of the anchoring position of the linker was determined by the study of the residual antiprion activity of the corresponding 6AP or GA conjugates. Very recently, these two affinity matrices were used for chromatography assays leading to the identification of ribosome (via the rRNA) as a common target of these two antiprion drugs. Here, we show, using competition experiments with Quinacrine (QC) and Chlorpromazine (CPZ), two other antiprion drugs, that QC, but not CPZ, may also directly target the rRNA.
描述了两种不相关的朊病毒抑制剂 6-氨基菲啶（6AP）和 2,6-二氯苯亚甲基氨基胍（Guanabenz，GA）的亲和基质的合成。在这两种情况下，都通过 Mitsunobu 反应引入相同的简单间隔物 ε-氨基己酰氨基戊醇，并且通过研究相应的 6AP 或 GA 缀合物的残余抗朊病毒活性来确定连接子的锚固位置。最近，这两种亲和基质被用于色谱分析，从而鉴定核糖体（通过 rRNA）是这两种抗朊病毒药物的共同靶标。在这里，我们使用 Quinacrine（QC）和 Chlorpromazine（CPZ）这两种其他抗朊病毒药物的竞争实验表明，QC 可能也直接靶向 rRNA，但 CPZ 不会。
