Riboswitches as antibacterial drug targets

被引：0
作者：
Kenneth F Blount
Ronald R Breaker
机构：
[1] Cellular and Developmental Biology,Department of Molecular
[2] Yale University,Department of Molecular Biophysics and Biochemistry
[3] Yale University,undefined
[4] Howard Hughes Medical Institute,undefined
[5] Yale University,undefined
来源：
Nature Biotechnology | 2006年 / 24卷
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摘要：
New validated cellular targets are needed to reinvigorate antibacterial drug discovery. This need could potentially be filled by riboswitches—messenger RNA (mRNA) structures that regulate gene expression in bacteria. Riboswitches are unique among RNAs that serve as drug targets in that they have evolved to form structured and highly selective receptors for small drug-like metabolites. In most cases, metabolite binding to the receptor represses the expression of the gene(s) encoded by the mRNA. If a new metabolite analog were designed that binds to the receptor, the gene(s) regulated by that riboswitch could be repressed, with a potentially lethal effect to the bacteria. Recent work suggests that certain antibacterial compounds discovered decades ago function at least in part by targeting riboswitches. Herein we will summarize the experiments validating riboswitches as drug targets, describe the existing technology for riboswitch drug discovery and discuss the challenges that may face riboswitch drug discoverers.
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页码：1558 / 1564
页数：6
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共 188 条
[31]  
Forsyth RA(1958)Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand Arch. Biochem. Biophys. 77 372-377
[32]  
Dunman PM(1957)Structure of the J. Am. Chem. Soc. 79 5693-5696
[33]  
Epshtein V(2003)-adenosylmethionine riboswitch regulatory mRNA element Genes Dev. 17 2688-2697
[34]  
Mironov AS(1975)Molecular-recognition characteristics of SAM-binding riboswitches J. Bacteriol. 121 970-974
[35]  
Nudler E(1992)The pyridine analog of thiamine and the growth of fungi FEMS Microbiol. Lett. 71 23-27
[36]  
Murphy BA(1982)Selective reversible inhibition of microbial growth with pyrithiamine Agric. Biol. Chem. 46 2003-2008
[37]  
Grundy FJ(1977)Formation of thiamine pyrophosphate in brain tissue Bioorg. Khim 3 521-524
[38]  
Henkin TM(1999)Inhibition of lysine utilization in bacteria by Trends Genet. 15 439-442
[39]  
Winkler WC(2002)-(beta-aminoethyl) cysteine and its reversal by lysine peptides Proc. Natl. Acad. Sci. USA 99 15908-15913
[40]  
Nahvi A(2004)-4-oxalysine, an inhibitory analog of lysine Appl. Environ. Microbiol. 70 5769-5777
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