Probing surface structure of sarcin domain on ribosomes ofEscherichia coli by complementary oligo DNAs and ribosome-inactivating protein

Cheung, Jin-I.; Lin, Alan

doi:10.1007/bf02253569

Cited by 1 publication

(2 citation statements)

References 34 publications

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“…As described in section 2, the asODNs have mainly been used in cell-free or cell extract assays to determine accessible target sites in mRNAs as well as studying topology of ribosomal RNAs [ 141 - 144 ]. However, ODNs have been used in antimicrobial studies as well.…”

Section: Antisense Oligonucleotides Analogues and Mimicsmentioning

confidence: 99%

Hitting bacteria at the heart of the central dogma: sequence-specific inhibition

2007

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An important objective in developing new drugs is the achievement of high specificity to maximize curing effect and minimize side-effects, and high specificity is an integral part of the antisense approach. The antisense techniques have been extensively developed from the application of simple long, regular antisense RNA (asRNA) molecules to highly modified versions conferring resistance to nucleases, stability of hybrid formation and other beneficial characteristics, though still preserving the specificity of the original nucleic acids. These new and improved second-and thirdgeneration antisense molecules have shown promising results. The first antisense drug has been approved and more are in clinical trials. However, these antisense drugs are mainly designed for the treatment of different human cancers and other human diseases. Applying antisense gene silencing and exploiting RNA interference (RNAi) are highly developed approaches in many eukaryotic systems. But in bacteria RNAi is absent, and gene silencing by antisense compounds is not nearly as well developed, despite its great potential and the intriguing possibility of applying antisense molecules in the fight against multiresistant bacteria. Recent breakthrough and current status on the development of antisense gene silencing in bacteria including especially phosphorothioate oligonucleotides (PS-ODNs), peptide nucleic acids (PNAs) and phosphorodiamidate morpholino oligomers (PMOs) will be presented in this review.

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Section: Antisense Oligonucleotides Analogues and Mimicsmentioning

confidence: 99%

Hitting bacteria at the heart of the central dogma: sequence-specific inhibition

2007

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“…Nevertheless since the 1970s, antisense molecules, particularly DNA, complementary to exposed regions of rRNA, have been used to study ribosomes. They have been useful in determining accessibility maps of rRNA, − quaternary structure, − and functional regions of the ribosome . As a consequence of these functional studies, it has been established that oligonucleotides are capable of inhibiting ribosome function by acting as steric hindrances.…”

Section: Approaches Used To Identify or Design New Antibioticsmentioning

confidence: 99%

Using Sequence-Specific Oligonucleotides To Inhibit Bacterial rRNA

2013

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The majority of antibiotics used in the clinic target bacterial protein synthesis. However, the widespread emergence of bacterial resistance to existing drugs creates a need to discover or develop new therapeutic agents. Ribosomal RNA (rRNA) has been a target for numerous antibiotics that bind to functional rRNA regions such as the peptidyl transferase center, polypeptide exit tunnel, and tRNA binding sites. Even though the atomic resolution structures of many ribosome-antibiotic complexes have been solved, improving the ribosome-acting drugs is difficult because the large rRNA has a complicated 3D architecture and is surrounded by numerous proteins. Computational approaches, such as structure-based design, often fail when applied to rRNA binders because electrostatics dominate the interactions and the effect of ions and bridging waters is difficult to account for in the scoring functions. Improving the classical anti-ribosomal agents has not proven particularly successful and has not kept pace with acquired resistance. So one needs to look for other ways to combat the ribosomes, finding either new rRNA targets or totally different compounds. There have been some efforts to design translation inhibitors that act on the basis of the sequence-specific hybridization properties of nucleic acid bases. Indeed oligonucleotides hybridizing with functional regions of rRNA have been shown to inhibit translation. Also, some peptides have been shown to be reasonable inhibitors. In this review we describe these nonconventional approaches to screening for ribosome inhibition and function of particular rRNA regions. We discuss inhibitors against rRNA that may be designed according to nucleotide sequence and higher order structure.

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Probing surface structure of sarcin domain on ribosomes ofEscherichia coli by complementary oligo DNAs and ribosome-inactivating protein

Cited by 1 publication

References 34 publications

Hitting bacteria at the heart of the central dogma: sequence-specific inhibition

Hitting bacteria at the heart of the central dogma: sequence-specific inhibition

Using Sequence-Specific Oligonucleotides To Inhibit Bacterial rRNA

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