Browse
Submit Data
Databases
API
Help

Dataset Information

40 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PNA containing isocytidine nucleobase: synthesis and recognition of double helical RNA.

ABSTRACT: Peptide nucleic acid (PNA1) containing a 5-methylisocytidine (iC) nucleobase has been synthesized. Triple helix formation between PNA1 and RNA hairpins having variable base pairs interacting with iC was studied using isothermal titration calorimetry. The iC nucleobase recognized the proposed target, C-G inversion in polypurine tract of RNA, with slightly higher affinity than the natural nucleobases, though the sequence selectivity of recognition was low. Compared to non-modified PNA, PNA1 had lower affinity for its RNA target.

SUBMITTER: Zengeya T

PROVIDER: S-EPMC3056986 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

PNA containing isocytidine nucleobase: synthesis and recognition of double helical RNA.

Zengeya Thomas T Li Ming M Rozners Eriks E

Bioorganic & medicinal chemistry letters 20110201 7

Peptide nucleic acid (PNA1) containing a 5-methylisocytidine (iC) nucleobase has been synthesized. Triple helix formation between PNA1 and RNA hairpins having variable base pairs interacting with iC was studied using isothermal titration calorimetry. The iC nucleobase recognized the proposed target, C-G inversion in polypurine tract of RNA, with slightly higher affinity than the natural nucleobases, though the sequence selectivity of recognition was low. Compared to non-modified PNA, PNA1 had lo ...[more]

PMID: 21333533

Similar Datasets

Triple helical recognition of pyrimidine inversions in polypurine tracts of RNA by nucleobase-modified PNA.

Project description:Peptide nucleic acids containing 2-pyrimidinone (P) and 3-oxo-2,3-dihydropyridazine (E) heterocycles recognized C-G and U-A inversions in a polypurine tract of double helical RNA with high affinity and sequence selectivity at pH 6.25. E-modified PNA bound strongly to bacterial A-site RNA, while no binding was observed to the human A-site RNA.

| S-EPMC3757498 | biostudies-literature

A solid-phase CuAAC strategy for the synthesis of PNA containing nucleobase surrogates.

Project description:The synthesis of an azide containing PNA monomer is described. The monomer was incorporated into two PNA sequences for the purpose of synthesizing an intercalating fluorophore-labeled PNA and a metal binding hairpin using a solid phase copper catalyzed azide-alkyne Huisgen cycloaddition (CuAAC). Click chemistry was performed using 2-ethynylfluorene or 1-ethynylpyrene to add a fluorophore to the PNA, which were tested for their ability to recognize an abasic site on a DNA target. A PNA hairpin possessing azide monomers at each termini was synthesized and reacted with 2-ethynylpyridine to form a hairpin that is stabilized by Ni²⁺.

| S-EPMC3654728 | biostudies-literature

Pyridazine Nucleobase in Triplex-Forming PNA Improves Recognition of Cytosine Interruptions of Polypurine Tracts in RNA.

Project description:Sequence specific recognition of regulatory noncoding RNAs would open new possibilities for fundamental science and medicine. However, molecular recognition of such complex double-stranded RNA (dsRNA) structures remains a formidable problem. Recently, we discovered that peptide nucleic acids (PNAs) form an unusually stable and sequence-specific triple helix with dsRNA. Triplex-forming PNAs could become universal tools for recognition of noncoding dsRNAs but are limited by the requirement of polypurine tracts in target RNAs as only purines form stable Hoogsteen hydrogen bonded base triplets. Herein, we systematically surveyed simple nitrogen heterocycles PN as modified nucleobases for recognition of cytosine in PN*C-G triplets. We found that a 3-pyridazinyl nucleobase formed significantly more stable PN*C-G triplets than other heterocycles including the pyrimidin-2-one previously used by us and others for recognition of cytosine interruptions in polypurine tracts of PNA-dsRNA triplexes. Our results improve triple helical recognition of dsRNA and provide insights for future development of new nucleobases to expand the sequence scope of noncoding dsRNAs that can be targeted by triplex-forming PNAs.

| S-EPMC8673316 | biostudies-literature

Triple-helical recognition of RNA using 2-aminopyridine-modified PNA at physiologically relevant conditions.

Project description:Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases form stable and sequence-selective triple helices with double-stranded RNA at physiologically relevant conditions. The M-modified PNA showed unique RNA selectivity by having two orders of magnitude higher affinity for the double-stranded RNAs than for the same DNA sequences.

| S-EPMC3756501 | biostudies-literature

Sequence selective recognition of double-stranded RNA at physiologically relevant conditions using PNA-peptide conjugates.

Project description:Conjugation of short peptide nucleic acids (PNA) with tetralysine peptides strongly enhanced triple helical binding to RNA at physiologically relevant conditions. The PNA hexamers and heptamers carrying cationic nucleobase and tetralysine modifications displayed high binding affinity for complementary double-stranded RNA without compromising sequence selectivity. The PNA-peptide conjugates had unique preference for binding double-stranded RNA, while having little, if any, affinity for double-stranded DNA. The cationic PNAs were efficiently taken up by HEK293 cells, whereas little uptake was observed for unmodified PNA.

| S-EPMC3745792 | biostudies-literature

Shape selective bifacial recognition of double helical DNA

Project description:An impressive array of antigene approaches has been developed for recognition of double helical DNA over the past three decades; however, few have exploited the ‘Watson–Crick’ base-pairing rules for establishing sequence-specific recognition. One approach employs peptide nucleic acid as a molecular reagent and strand invasion as a binding mode. However, even with integration of the latest conformationally-preorganized backbone design, such an approach is generally confined to sub-physiological conditions due to the lack of binding energy. Here we report the use of a class of shape-selective, bifacial nucleic acid recognition elements, namely Janus bases, for targeting double helical DNA or RNA. Binding occurs in a highly sequence-specific manner under physiologically relevant conditions. The work may provide a foundation for the design of oligonucleotides for targeting the secondary and tertiary structures of nucleic acid biopolymers.

| S-EPMC9923363 | biostudies-literature

The first crystal structures of RNA-PNA duplexes and a PNA-PNA duplex containing mismatches--toward anti-sense therapy against TREDs.

Project description:PNA is a promising molecule for antisense therapy of trinucleotide repeat disorders. We present the first crystal structures of RNA-PNA duplexes. They contain CUG repeats, relevant to myotonic dystrophy type I, and CAG repeats associated with poly-glutamine diseases. We also report the first PNA-PNA duplex containing mismatches. A comparison of the PNA homoduplex and the PNA-RNA heteroduplexes reveals PNA's intrinsic structural properties, shedding light on its reported sequence selectivity or intolerance of mismatches when it interacts with nucleic acids. PNA has a much lower helical twist than RNA and the resulting duplex has an intermediate conformation. PNA retains its overall conformation while locally there is much disorder, especially peptide bond flipping. In addition to the Watson-Crick pairing, the structures contain interesting interactions between the RNA's phosphate groups and the Π electrons of the peptide bonds in PNA.

| S-EPMC4770230 | biostudies-literature

Synthesis and biological properties of caffeic acid-PNA dimers containing guanine.

Project description:Caffeic acid (CA; 3,4-dihydroxycinnamic acid) is endowed with high antioxidant activity. CA derivatives (such as amides) have gained a lot of attention due to their antioxidative, antitumor and antimicrobial properties as well as stable characteristics. Caffeoyl-peptide derivatives showed different antioxidant activity depending on the type and the sequence of amino acid used. For these reasons, we decided to combine CA with Peptide Nucleic Acid (PNA) to test whether the new PNA-CA amide derivatives would result in an improvement or gain of CA's biological (i.e., antioxidant, cytotoxic, cytoprotective) properties. We performed the synthesis and characterization of seven dimer conjugates with various combinations of nucleic acid bases and focused NMR studies on the model compound ga-CA dimer. We demonstrate that PNA dimers containing guanine conjugated to CA exhibited different biological activities depending on composition and sequence of the nucleobases. The dimer ag-CA protected HepG2, SK-B-NE(2), and C6 cells from a cytotoxic dose of hydrogen peroxide (H₂O₂).

| S-EPMC6270098 | biostudies-literature

Sequence-selective recognition of double-stranded RNA and enhanced cellular uptake of cationic nucleobase and backbone-modified peptide nucleic acids.

Project description:Sequence-selective recognition of complex RNAs in live cells could find broad applications in biology, biomedical research, and biotechnology. However, specific recognition of structured RNA is challenging, and generally applicable and effective methods are lacking. Recently, we found that peptide nucleic acids (PNAs) were unusually well-suited ligands for recognition of double-stranded RNAs. Herein, we report that 2-aminopyridine (M) modified PNAs and their conjugates with lysine and arginine tripeptides form strong (Ka = 9.4 to 17 × 107 M-1) and sequence-selective triple helices with RNA hairpins at physiological pH and salt concentration. The affinity of PNA-peptide conjugates for the matched RNA hairpins was unusually high compared to the much lower affinity for DNA hairpins of the same sequence (Ka = 0.05 to 1.1 × 107 M-1). The binding of double-stranded RNA by M-modified PNA-peptide conjugates was a relatively fast process (kon = 2.9 × 104 M-1 sec-1) compared to the notoriously slow triple helix formation by oligodeoxynucleotides (kon ∼ 103 M-1 sec-1). M-modified PNA-peptide conjugates were not cytotoxic and were efficiently delivered in the cytosol of HEK293 cells at 10 µM. Surprisingly, M-modified PNAs without peptide conjugation were also taken up by HEK293 cells, which, to the best of our knowledge, is the first example of heterocyclic base modification that enhances the cellular uptake of PNA. Our results suggest that M-modified PNA-peptide conjugates are promising probes for sequence-selective recognition of double-stranded RNA in live cells and other biological systems.

| S-EPMC5159649 | biostudies-literature

Intrastrand backbone-nucleobase interactions stabilize unwound right-handed helical structures of heteroduplexes of L-aTNA/RNA and SNA/RNA.

Project description:Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH-O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.

| S-EPMC9814321 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data