Molecular Recognition of RNA by Neomycin and a Restricted Neomycin Derivative

Zhao, Fang; Zhao, Qiang; Blount, Ken; Han, Qing; Tor, Yitzhak; Hermann, Thomas

doi:10.1002/anie.200500903

Cited by 83 publications

(59 citation statements)

References 33 publications

(36 reference statements)

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“…21,22 Recent structural and biochemical studies have suggested a potential mechanism by which aminoglycosides achieve their antitranslational effects. 23,12,[24][25][26][27][28]13,29,14,19,30,15 According to this mechanism, A1492 and A1493 are in conformational equilibria between intrahelical and extrahelical states. When in their extrahelical states, both bases engage in interactions with minihelix formed by the mRNA codon and the tRNA anticodon.…”

Section: Greater Extents Of Aminoglycoside-induced Reduction In the Mmentioning

confidence: 99%

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

2007

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Spectroscopic and calorimetric techniques have been employed to characterize the impact of incorporation of the fluorescent base analog 2-aminopurine into the 1492 or 1493 position of an E. coli rRNA A-site model oligonucleotide, as well as the energetics and dynamics associated with recognition of this A-site model oligomer by aminoglycoside antibiotics. The results of these studies indicate that incorporation of 2AP into either the 1492 or 1493 position does not perturb the structure or stability of the host RNA or its aminoglycoside binding affinity. In addition, the results also highlight drug-induced reduction in the mobilities of the bases at both positions 1492 and 1493 as a potentially key determinant of bactericidal potency.

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Section: Greater Extents Of Aminoglycoside-induced Reduction In the Mmentioning

confidence: 99%

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

2007

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“…The reported crystal structures of aminoglycoside-RNA complexes 20,[22][23][24][25][26][27][28][29] reveal an important hydrogen bond between 6′-NH 2 and N1 of A1408. Moreover, the antibacterial activity of aminoglycosides containing a 6′-OH suggests that hydrogen bonding at the 6′ position may be more important than the electrostatic binding to RNA.…”

Section: Design and Synthesis Of Neamine Derivativesmentioning

confidence: 99%

The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity

Yan

Gao

Yotphan

et al. 2007

Bioorganic & Medicinal Chemistry

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Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding between 6′-NH 2 and 16S rRNA for antibacterial activity.

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“…A conformationally constrained neomycin analogue 27 (Figure 21, left), originally designed to target the bacterial ribosomal A site and the HIV-1 TAR sequences [129,130] was shown to bind the HIV-1 subtype F DIS kissing-loop (K d = 1.9 mm). [122] The idea of this approach is to restrict possible conformations of the free drug in solution in order to reduce the negative entropic contribution for binding, and thus enhance the affinity.…”

Section: Rev-rre Interactionmentioning

confidence: 99%

The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study

et al. 2014

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The human immunodeficiency virus 1 (HIV-1) replication cycle is finely tuned with many important steps involving RNA-RNA or protein-RNA interactions, all of them being potential targets for the development of new antiviral compounds. This cycle can also be considered as a good benchmark for the evaluation of early-stage strategies aiming at designing drugs that bind to RNA, with the possibility to correlate in vitro activities with antiviral properties. In this review, we highlight different approaches developed to interfere with four important steps of the HIV-1 replication cycle: the early stage of reverse transcription, the transactivation of viral transcription, the nuclear export of partially spliced transcripts and the dimerization step.

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Molecular Recognition of RNA by Neomycin and a Restricted Neomycin Derivative

Cited by 83 publications

References 33 publications

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity

The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study

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