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Inhibiting RNA-protein interactions with branched peptide boronic acids

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If you have a question about this talk, please contact M. Madan Babu.

Many important functions of RNA result from specific proteins binding to complex tertiary structures of RNA . One such example is evident in the HIV -1 transactivation response element region (TAR) RNA , a conserved 59-nucleotide stem loop located at the 5’ end of all nascent transcribed HIV -1 mRNA. Binding of the transcriptional activator protein Tat and the cyclin T1/cdk1 kinase complex promotes efficient transcriptional elongation. Another RNA , RRE , plays a vital role in RNA splicing and the Rev protein is essential for its export from the nucleus. Disruption of Tat-TAR or Rev-RRE interaction results in the blockade of viral replication and thus represents a viable strategy in developing new anti-HIV therapeutics. We recently screened a library of branched peptides and discovered selective binders for HIV -1 RNAs. We will discuss the cell permeability, cell toxicity, in-vitro inhibition assay utilizing a firefly luciferase system of these branched peptides as well as the development of branched peptide boronic acids as the next generation inhibitors.

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