Selected article for: "cell culture and viral rna"
Author: Morgan, Brittany S; Forte, Jordan E; Hargrove, Amanda E
Title: Insights into the development of chemical probes for RNA
  • Document date: 2018_9_19
    • ID: wupre5uj_6
    Snippet: The 116 chemical probes targeted 33 distinct RNA elements, including those from bacterial, fungal, human, or viral systems [ Figure 1 ]. Although some overlap between targets was observed, the small molecules probed a wider range of RNAs in cell culture than the multivalent ligands [ Figure 1A ]. The most common small molecule target was the HIV-1 Trans-activation response element (TAR) RNA, a well-studied and frequently screened RNA that binds t.....
    Document: The 116 chemical probes targeted 33 distinct RNA elements, including those from bacterial, fungal, human, or viral systems [ Figure 1 ]. Although some overlap between targets was observed, the small molecules probed a wider range of RNAs in cell culture than the multivalent ligands [ Figure 1A ]. The most common small molecule target was the HIV-1 Trans-activation response element (TAR) RNA, a well-studied and frequently screened RNA that binds to the viral protein Tat (23) . Disruption of this interaction reduces viral production and represents an alternative strategy against HIV. Some of the first RNA-targeted chemical probes were developed for TAR RNA, including a tetraaminoquinozaline (28) and a 6-aminoquinolone (29, 30) with an EC 50 value of 16 M and an IC 50 value of 0.85 M, respectively, in chronically infected HIV cell models. On the other hand, only one bioactive small molecule was identified for a fungal target, specifically the Candida albicans LSU Group 1 Ribozyme (31). This essential ribozyme is a desirable antifungal target as it leads to failed ribosomal assembly when mutated and is absent in the human genome. Further, 10/75 small molecule chemical probes demonstrated efficacy in animal models, targeting seven unique RNA elements in bacterial and human systems. One recent example (19) targeted the G-quadruplex structure located in the 5 -untranslated region (UTR) of Human Vascular Endothelial Growth Factor (hVEGF) mRNA, an angiogenic growth factor involved in tumor progression. In a breast cancer mouse model, the small molecule showed antitumor efficacy similar to that of doxorubicin but with fewer indications of side effects.

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