Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase

Lee, Jeeyeon; Kang, Sang Uk; Kang, Mee Kyoung; Chun, Moon Woo; Jo, Yeong Joon; Kkwak, Jin Hwan; Kim, Sung Hoon

doi:10.1016/s0960-894x(99)00206-1

Cited by 39 publications

(15 citation statements)

References 11 publications

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“…These compounds showed good selectivity versus human MetRS but lacked antibacterial activity in whole-cell assays. Other methionine analogs have shown much weaker MetRS inhibition, with K i values in the low micromolar range and a very narrow antibacterial spectrum (24,25). The 2-pyridyl-pyrazoles (14) demonstrated moderate biochemical potency and selectivity but exhibited off-target activity in whole-cell assays.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

Green

Bullard

Ribble

et al. 2009

Antimicrob Agents Chemother

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Section: Resultsmentioning

confidence: 99%

Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

Green

Bullard

Ribble

et al. 2009

Antimicrob Agents Chemother

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“…Loading of Met-tRNA i Met onto 40S subunits requires methionyl-tRNA synthetase to provide a dedicated pool of Met-tRNA i Met for AUG initiation [23]. Inhibitors of methionyl-tRNA synthetase block initiation at AUG start codons with Met-tRNA i Met because they inhibit aminoacylation of tRNA with methionine [24]. We used methionine sulfamide (Met-sulfamide), a synthetic methionyl-tRNA synthetase inhibitor in the AUG versus CUG toeprint assay.…”

Section: Resultsmentioning

confidence: 99%

A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

Starck

Jiang

et al. 2008

PLoS ONE

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MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance.

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“…The bisubstrate inhibitor 20 has been reported as a moderate mycobacterial methionyl-tRNA synthase inhibitor ( Figure 6B) [81,82]. Unfortunately this compound did not show activity in in vitro whole-cell assays.…”

Section: Aryl Acid Adenylating Enzyme (Mbta)mentioning

confidence: 98%

Nucleoside Analogs and Tuberculosis: New Weapons Against an Old Enemy

Ferrari

Serpi

2015

Future Med. Chem.

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Purine and pyrimidine nucleoside and nucleotide analogs have been extensively studied as anticancer and antiviral agents. In addition to this, they have recently shown great potential against Mycobacterium Tuberculosis, the causative agent of TB. TB ranks as the tenth most common cause of death in the world. The current treatment for TB infection is limited by side effects and cost of the drugs and most importantly by the development of resistance to the therapy. Therefore the development of novel drugs, capable of overcoming the drawbacks of the existing treatments, has become the focus of many research programs. In parallel to that, a tremendous effort has been made to elucidate the unique metabolism of this pathogen with the aim to identify new possible targets. This review presents the state of the art in nucleoside and nucleotide analogs in the treatment of TB. In particular, we report on the inhibitory activity of this class of compounds, both in enzymatic and whole-cell assays, providing a brief insight to which reported target these novel compounds are hitting.

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Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase

Cited by 39 publications

References 11 publications

Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

Nucleoside Analogs and Tuberculosis: New Weapons Against an Old Enemy

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