Targeting RNA-Protein Interactions within the Human Immunodeficiency Virus Type 1 Lifecycle

被引：31

作者：

Bell, Neil M. ^{[1
,2
]}

L'Hernault, Anne ^{[2
]}

Murat, Pierre ^{[1
]}

Richards, James E. ^{[2
]}

Lever, Andrew M. L. ^{[2
]}

Balasubramanian, Shankar ^{[1
,3
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[2] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England

[3] Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

来源：

BIOCHEMISTRY | 2013年 / 52卷 / 51期

基金：

英国医学研究理事会;

关键词：

HIV-1 PACKAGING SIGNAL; GAG; INHIBITOR; BINDING; SITE; 33258-HOECHST; GLYCOPROTEIN; REQUIREMENT; ENTRY; LOOP;

D O I：

10.1021/bi401270d

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Psi), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and Psi. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by H-1 NMR spectroscopy.

引用

页码：9269 / 9274

页数：6

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