Gudasheva T A, Deeva O A, Mokrov G V, Yarkov S A, Yarkova M A, Seredenin S B
Zakusov Research Institute of Pharmacology, ul. Baltiiskaya 8, Moscow, 125315, Russia.
Dokl Biochem Biophys. 2015;464:290-3. doi: 10.1134/S1607672915050063. Epub 2015 Oct 31.
On the basis of the structure of Alpidem, a pyrazolopyrimidine ligand of the translocator protein (TSPO), a dipeptide TSPO ligand, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), was designed and synthesized using our own original peptide design strategy. This compound exhibited anxiolytic activity in BALB/cAnN mice in the "open-field" test and in outbred CD1 mice in the "elevated plus maze" test. The stereoselectivity of the anxiolytic effect of GD-23 is demonstrated. The results of this study suggest that GD-23 is a ligand of the translocator protein, and its structure can become the basis for creating anxiolytics with a fundamentally new mechanism of action.
基于易位蛋白（TSPO）的吡唑并嘧啶配体阿尔皮地姆的结构，利用我们自己独创的肽设计策略设计并合成了一种二肽TSPO配体N-苄氧羰基-L-色氨酰-L-异亮氨酸酰胺（GD-23）。该化合物在“旷场”试验中的BALB/cAnN小鼠以及“高架十字迷宫”试验中的远交群CD1小鼠中均表现出抗焦虑活性。证明了GD-23抗焦虑作用的立体选择性。本研究结果表明，GD-23是易位蛋白的一种配体，其结构可成为开发具有全新作用机制的抗焦虑药物的基础。
