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RNA Targets (rna + target)

Distribution by Scientific Domains

Chemistry	80%

Selected Abstracts

2,- N -(Pyren-1-yl)acetyl-2,-Amino-,-L-LNA: Synthesis and Detection of Single Nucleotide Mismatches in DNA and RNA Targets

CHEMBIOCHEM, Issue 10 2007
T. Santhosh Kumar
Precise positioning of intercalators furnishes a SNP-detection tool. The conformationally locked 2-oxo-5-azabicyclo-[2.2.1]heptane skeleton of 2,-amino-,-L-LNA monomer X directs the N2,-linked pyrene moiety into nucleic acid duplex cores to give highly stabilized duplexes. We have used this precise positioning of pyrene moieties to develop probes that signal the presence of single-nucleotide mismatches in DNA/RNA targets by excimer signal formation. [source]

Highly Fluorescent Conjugated Pyrenes in Nucleic Acid Probes: (Phenylethynyl)pyrenecarbonyl-Functionalized Locked Nucleic Acids

CHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2008
Irina
Abstract In recent years, fluorescently labeled oligonucleotides have become a widely used tool in diagnostics, DNA sequencing, and nanotechnology. The recently developed (phenylethynyl)pyrenes are attractive dyes for nucleic acid labeling, with the advantages of long-wave emission relative to the parent pyrene, high fluorescence quantum yields, and the ability to form excimers. Herein, the synthesis of six (phenylethynyl)pyrene-functionalized locked nucleic acid (LNA) monomers M1,M6 and their incorporation into DNA oligomers is described. Multilabeled duplexes display higher thermal stabilities than singly modified analogues. An increase in the number of phenylethynyl substituents attached to the pyrene results in decreased binding affinity towards complementary DNA and RNA and remarkable bathochromic shifts of absorption/emission maxima relative to the parent pyrene fluorochrome. This bathochromic shift leads to the bright fluorescence colors of the probes, which differ drastically from the blue emission of unsubstituted pyrene. The formation of intra- and interstrand excimers was observed for duplexes that have monomers M1,M6 in both complementary strands and in numerous single-stranded probes. If more phenylethynyl groups are inserted, the detected excimer signals become more intense. In addition, (phenylethynyl)pyrenecarbonyl,LNA monomers M4, M5, and M6 proved highly useful for the detection of single mismatches in DNA/RNA targets. [source]

Metal-Assisted Hybridization of Oligonucleotides, Evaluation of Circular 2,- O -Me RNA as Ligands for the TAR RNA Target

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2003
Laurence Zapata
Abstract Two complementary oligonucleotides were conjugated with terpyridine ligands at their nearby 5,- and 3,-ends. Addition of a stoichiometric amount of a transition metal (Zn2+, Fe2+) resulted in a large increase in the melting temperature of the duplex. The conjugation of TPY to stem-loop oligomers provided an efficient procedure for the cyclisation of the oligomer after the addition of metal ions. Such a short stem-loop oligomer was designed to target the HIV-1 TAR RNA through loop,loop interactions. The addition of Zn2+ ions yielded a good ligand (Kd = 30 nM) for this RNA structural element. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

2,- N -(Pyren-1-yl)acetyl-2,-Amino-,-L-LNA: Synthesis and Detection of Single Nucleotide Mismatches in DNA and RNA Targets

Structure of the HIV-1 Rev response element alone and in complex with regulator of virion (Rev) studied by atomic force microscopy

FEBS JOURNAL, Issue 15 2009
Jesper Pallesen
The interaction of multiple HIV-1 regulator of virion (Rev) proteins with the viral RNA target, the Rev response element (RRE), is critical for nuclear export of incompletely spliced and unspliced viral RNA, and for the onset of the late phase in the viral replication cycle. The heterogeneity of the Rev,RRE complex has made it difficult to study using conventional structural methods. In the present study, atomic force microscopy is applied to directly visualize the tertiary structure of the RRE RNA alone and in complex with Rev proteins. The appearance of the RRE is compatible with the earlier proposed RRE secondary structure in dimensions and overall shape, including a stalk and a head interpreted as stem I, and stem-loops II,V in the secondary structure model, respectively. Atomic force microscopy imaging of the Rev,RRE complex revealed an increased height of the structure both in the stalk and head regions, which is in accordance with a binding model in which Rev binding to a high affinity site in stem IIB triggers oligomerization of Rev proteins through cooperative binding along stem I in RRE. The present study demonstrates that atomic force microscopy comprises a useful technique to study complex biological structures of nucleic acids at high resolution. [source]

Solution structures and characterization of human immunodeficiency virus Rev responsive element IIB RNA targeting zinc finger proteins,

BIOPOLYMERS, Issue 4 2006
Subrata H. Mishra
Abstract The Rev responsive element (RRE), a part of unspliced human immunodeficiency virus (HIV) RNA, serves a crucial role in the production of infectious HIV virions. The viral protein Rev binds to RRE and facilitates transport of mRNA to the cytoplasm. Inhibition of the Rev,RRE interaction disrupts the viral life cycle. Using a phage display protocol, dual zinc finger proteins (ZNFs) were generated that bind specifically to RREIIB at the high affinity Rev binding site. These proteins were further shortened and simplified, and they still retained their RNA binding affinity. The solution structures of ZNF29 and a mutant, ZNF29G29R, have been determined by nuclear magnetic resonance (NMR) spectroscopy. Both proteins form C2H2 -type zinc fingers with essentially identical structures. RNA protein interactions were evaluated quantitatively by isothermal titration calorimetry, which revealed dissociation constants (Kd's) in the nanomolar range. The interaction with the RNA is dependent upon the zinc finger structure; in the presence of EDTA, RNA binding is abolished. For both proteins, RNA binding is mediated by the ,-helical portion of the zinc fingers and target the bulge region of RREIIB-TR. However, ZNF29G29R exhibits significantly stronger binding to the RNA target than ZNF29; this illustrates that the binding of the zinc finger scaffold is amenable to further improvements. © 2006 Wiley Periodicals, Inc. Biopoly 83:352,364, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

A Tale of Two Targets: Differential RNA Selectivity of Nucleobase,Aminoglycoside Conjugates

CHEMBIOCHEM, Issue 10 2006
Kenneth F. Blount Dr.
Aminoglycoside antibiotics are RNA-binding polyamines that can bind with similar affinities to structurally diverse RNA targets. To design new semisynthetic aminoglycosides with improved target selectivity, it is important to understand the energetic and structural basis by which diverse RNA targets recognize similar ligands. It is also imperative to discover how novel aminoglycosides could be rationally designed to have enhanced selectivity for a given target. Two RNA drug targets, the prokaryotic ribosomal A-site and the HIV-1 TAR, provide an excellent model system in which to dissect the issue of target selectivity, in that they each have distinctive interactions with aminoglycosides. We report herein the design, synthesis, and binding activity of novel nucleobase,aminoglycoside conjugates that were engineered to be more selective for the A-site binding pocket. Contrary to the structural design, the conjugates bind the A-site more weakly than does the parent compound and bind the TAR more tightly than the parent compound. This result implies that the two RNA targets differ in their ability to adapt to structurally diverse ligands and thus have inherently different selectivities. This work emphasizes the importance of considering the inherent selectivity traits of the RNA target when engineering new ligands. [source]

FMRP RNA targets: identification and validation

GENES, BRAIN AND BEHAVIOR, Issue 6 2005
J. C. Darnell
The Fragile X Syndrome is caused by the loss of function of the FMR1 gene (Pieretti et al. 1991. Cell 66, 817,822; O'Donnell & Warren 2002. Annu Rev Neurosci 25, 315,338]. Identification of the RNA targets to which FMRP binds is a key step in understanding the function of the protein and the cellular defects caused by its absence (Darnell et al. 2004 Ment Retard Dev Disabil Res Rev 10, 49,52). Here we discuss the current understanding of FMRP as an RNA-binding protein, the different approaches that have been taken to identify FMRP RNA targets and the relevance of some of these approaches to FMRP biology. In addition, we present evidence that point mutations in the K-homology (KH)1 or KH2 domains of FMRP abrogate its polyribosome association in transfected neuroblastoma cells but that the deletion of the RGG box does not. This suggests that RNA binding by the RGG box of FMRP may mediate other aspects of cellular mRNA metabolism such as mRNA localization or that it may have a role downstream of polyribosome association. [source]

C5-Functionalized LNA: Unparalleled Hybridization Properties and Enzymatic Stability

CHEMBIOCHEM, Issue 17 2009
Michael E. Østergaard
The best of both worlds: C5-functionalized locked nucleic acids (LNAs) synergistically combine the beneficial features of C5-alkynyl DNAs and conventional antisense LNA,they are straightforward to make and yet exhibit unparalleled thermal affinity toward RNA targets, extraordinary discrimination of singly mismatched RNA strands, and superb stability against degradation by 3,-exonucleases. [source]

A Tale of Two Targets: Differential RNA Selectivity of Nucleobase,Aminoglycoside Conjugates

Cover Picture: Targeting RNA with Small Molecules (ChemBioChem 10/2003)

CHEMBIOCHEM, Issue 10 2003
Yitzhak Tor Prof. Dr.
Abstract The cover picture shows the processes involved in the search for small molecules as potent and selective RNA binders. Motivation comes from the desire to control cell function at the RNA level and to identify novel approaches to specifically combat pathogens by targeting their unique RNA sequences or RNA,protein complexes. Inspiration comes from nature; in particular, from aminoglycosides, a family of naturally occurring antibiotics that has been shown to target the bacterial ribosome. The discovery process involves identifying RNA targets (schematically shown as a ribosome or a virus), devising unique assays (e.g. a solid-phase assay), and generating the necessary knowledge and lead structures through design, synthesis, and systematic evaluation of biological activity. Further details can be found in the article by Y. Tor on p. 998 ff. [source]

Metallotherapeutics: Novel Strategies in Drug Design

CHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2009
Lalintip Hocharoen
Abstract A new paradigm for drug activity is presented, which includes both recognition and subsequent irreversible inactivation of therapeutic targets. Application to both RNA and protein biomolecules has been demonstrated. In contrast to RNA targets that are subject to strand scission chemistry mediated by ribose H-atom abstraction, proteins appear to be inactivated either through oxidative damage to amino acid side chains around the enzyme active site, or by backbone hydrolysis. [source]