Binding of an aminoacridine derivative to a GAAA RNA tetraloop

Yan, Zhaohui; Baranger, Anne M.

doi:10.1016/j.bmcl.2004.09.021

Cited by 14 publications

(19 citation statements)

References 48 publications

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“…RNAs are versatile molecules that play essential role in many biological processes and consequently the opportunity of drugs targeting are abundant. The naturally occurring aminoglycoside antibiotics have been one group of compounds found to bind to numerous RNA constructs [3]. Ribosomal RNA has also long been known to be receptor for antibiotics and antisense oligonucleotides can be used to down regulate gene expression [4].…”

Section: Introductionmentioning

confidence: 99%

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Giri

Hossain

Kumar

2006

International Journal of Biological Macromolecules

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Section: Introductionmentioning

confidence: 99%

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Giri

Hossain

Kumar

2006

International Journal of Biological Macromolecules

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“…It has been well documented that both QC and 9AA can intercalate into double-stranded DNA and structured RNA molecules (31,34,44) and are capable of inhibiting DNA replication, RNA transcription, and protein synthesis (7,10,26,29). The extent of intercalation of QC into RNA molecules depends on the complexity of RNA secondary and tertiary structures (such as hairpin loops that produce regions of double-stranded RNA) and pseudoknots (2,52). QC has also been shown to inhibit protein synthesis in a cell-free translation system either by inhibiting the peptidyl transferase activity of the ribosome or by preventing binding of mRNAs to the ribosome (28).…”

mentioning

confidence: 99%

Inhibition of Encephalomyocarditis Virus and Poliovirus Replication by Quinacrine: Implications for the Design and Discovery of Novel Antiviral Drugs

Gasparian

Neznanov

Jha

et al. 2010

J Virol

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The 9-aminoacridine (9AA) derivative quinacrine (QC) has a long history of safe human use as an antiprotozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results suggest that QC and similar intercalating drugs could potentially be used for treatment of viral infections.

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“…The flexible side chain of AD1 may allow it to interact with multiple RNA binding sites. We and others have shown that AD1 binds to stem-loop 2 of U1 snRNA, 50 HIV-1 TAR RNA, 56,87 tetraloop RNA, 54 and duplex RNA. 57 The rigidity of the side chain of AD2 relative to that of AD1 may be responsible for the increased selectivity of RNA binding.…”

Section: Resultsmentioning

confidence: 97%

Identification of an Aminoacridine Derivative That Binds to RNA Tetraloops

et al. 2007

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RNA folds into diverse structures that form unique targets for small molecules and thus provide significant potential for controlling biological processes involving RNA with small-molecule ligands. We are investigating molecular recognition of tetraloop RNA by small molecules. RNA tetraloops are four-nucleotide stem loops with unusual stability that are involved in biological processes involving RNA by forming binding sites for proteins and other RNAs. We have sequentially used the docking programs DOCK and AutoDock to screen 1990 small molecules in the NCI diversity set to identify molecules selective for RNA tetraloops over double-stranded RNA. The compounds predicted to bind to tetraloop RNA were evaluated for binding RNA tetraloops using 1H NMR spectroscopy and fluorescence techniques. An aminoacridine derivative (AD2) was identified that binds to a GAAA tetraloop in a 2:1 ratio with dissociation constants of 1.0 and 4.0 microM. AD2 binds with approximately 20-fold and 9-fold higher affinity to tetraloop RNA than to double- and single-stranded RNAs, respectively.

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Binding of an aminoacridine derivative to a GAAA RNA tetraloop

Cited by 14 publications

References 48 publications

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Inhibition of Encephalomyocarditis Virus and Poliovirus Replication by Quinacrine: Implications for the Design and Discovery of Novel Antiviral Drugs

Identification of an Aminoacridine Derivative That Binds to RNA Tetraloops

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