Arginine‐aminoglycoside conjugates that bind to HIV transactivation responsive element RNA in vitro

FEBS Letters

Lapidot, Aviva²  Evdokimov, Artem G¹  Litovchick, Alexander² 

[1] Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel

关键词: Aminoglycoside-arginine conjugate;    Transactivation responsive element RNA binder;    HIV Tat/transactivation responsive element inhibition;    Drug design;   

DOI  :  10.1016/S0014-5793(99)00092-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

HIV gene expression is crucially dependent on binding of the viral Tat protein to the transactivation RNA response element. A number of synthetic Tat-transactivation responsive element interaction inhibitors of peptide/peptoid nature were described as potential antiviral drug prototypes. We present a new class of peptidomimetic inhibitors, conjugates of l-arginine with aminoglycosides. Using a gel-shift assay and affinity chromatography on an l-arginine column we found that these compounds bind specifically to the transactivation responsive element RNA in vitro with K _d values in the range of 20–400 nM, which is comparable to the K _d of native Tat bound to the transactivation responsive element (10–12 nM). Confocal microscopy studies demonstrated that fluorescein-labelled conjugate penetrates into live cells. High affinity to the transactivation responsive element, low toxicity, and relative simplicity of synthesis make these compounds attractive candidates for antiviral drug design.

【 授权许可】

Unknown