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Probing interaction of a fluorescent ligand with HIV TAR RNA.

Probing interaction of a fluorescent ligand with HIV TAR RNA.
Author Information (click to view)

Qi L, Zhang J, He T, Huo Y, Zhang ZQ,


Qi L, Zhang J, He T, Huo Y, Zhang ZQ, (click to view)

Qi L, Zhang J, He T, Huo Y, Zhang ZQ,

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Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 2016 08 30173() 93-98 pii 10.1016/j.saa.2016.08.058

Abstract

Trans-activator of Transcription (Tat) antagonists could block the interaction between Tat protein and its target, trans-activation responsive region (TAR) RNA, to inhibit Tat function and prevent human immunodeficiency virus type 1 (HIV-1) replication. For the first time, a small fluorescence ligand, ICR 191, was found to interact with TAR RNA at the Tat binding site and compete with Tat. It was also observed that the fluorescence of ICR 191 could be quenched when binding to TAR RNA and recovered when discharged via competition with Tat peptide or a well-known Tat inhibitor, neomycin B. The binding parameters of ICR 191 to TAR RNA were determined through theoretical calculations. Mass spectrometry, circular dichroism and molecular docking were used to further confirm the interaction of ICR 191 with TAR RNA. Inspired by these discoveries, a primary fluorescence model for the discovery of Tat antagonists was built using ICR 191 as a fluorescence indicator and the feasibility of this model was evaluated. This ligand-RNA interaction could provide a new strategy for research aimed at discovering Tat antagonists.

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