scholarly journals Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach

2020 ◽  
Vol 8 ◽  
Author(s):  
Maria Moccia ◽  
Flavia Anna Mercurio ◽  
Emma Langella ◽  
Valerio Piacenti ◽  
Marilisa Leone ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Uv Spectroscopy ◽  
Integrated Approach ◽  
Structural Features ◽  
Seed Region ◽  
Rna Sequences ◽  
Nmr Characterization ◽  
Rna Targeting ◽  
Fluorescent Tag

In the present work, structural features of the interaction between peptide nucleic acid (PNA)-based analogs of the tumor-suppressor microRNA-34a with both its binding sites on MYCN mRNA were investigated. In particular, the region from base 1 to 8 (“seed” region) of miR-34a was reproduced in the form of an 8-mer PNA fragment (tiny PNA), and binding to target 3'UTR MYCN mRNA, was studied by a seldom reported and detailed NMR characterization, providing evidence for the formation of anti-parallel duplexes with a well-organized structural core. The formation of PNA-3'UTR duplexes was also confirmed by Circular Dichroism, and their melting curves were measured by UV spectroscopy. Nevertheless, this study offered a valuable comparison between molecular dynamics predictions and experimental evidence, which showed great correlation. Preliminary uptake assays were carried out in Neuroblastoma Kelly cells, using short peptide conjugates as carriers and FITC fluorescent tag for subcellular localization. Moderate internalization was observed without the use of transfecting agents. The reported results corroborate the interest toward the design and development of chimeric PNA/RNA sequences as effective RNA-targeting agents.

The detrimental effect of orotic acid substitution in the peptide nucleic acid strand on the stability of PNA2:NA triple helices

2005 ◽  
Vol 83 (10) ◽  
pp. 1731-1740 ◽  
Author(s):  
Robert HE Hudson ◽  
Filip Wojciechowski
Keyword(s):  
Nucleic Acid ◽  
Carboxylic Acid ◽  
Peptide Nucleic Acid ◽  
Triple Helix ◽  
Orotic Acid ◽  
Uv Spectroscopy ◽  
Triplex Formation ◽  
Helix Formation ◽  
Triple Helix Formation ◽  
The Stability

We have investigated the incorporation of C6 derivatives of uracil into polypyrimidine peptide nucleic acid oligomers. Starting with uracil-6-carboxylic acid (orotic acid), a peptide nucleic acid monomer compatible with Fmoc-based synthesis was prepared. This monomer then served as a convertible nucleobase whereupon treatment of the resin-bound methyl orotate containing hexamers with hydroxide or amines cleanly converted the ester to an orotic acid or orotamide-containing peptide nucleic acid. Peptide nucleic acid hexamers containing the C6-modified nucleobase hybridized to both poly(riboadenylic acid) and poly(deoxyriboadenylic acid) via triplex formation. Complexes formed with poly(riboadenylic acid) were more stable than those formed with poly(dexoyriboadenylic acid), as measured by temperature-dependent UV spectroscopy. However, both of these complexes were destabilized relative to the complexes formed by an unmodified peptide nucleic acid oligomers. Internal or doubly substituted hexamers are destabilized more strongly than a terminally substituted one, and the type of substitution (carboxamide, ester, carboxylic acid) affects the overall triplex stability. These results clearly show that incorporation of a C6-substituted uracil into polypyrimidine PNA is detrimental to triplex formation. We have also extended this chemistry to incorporate uracil-5-methylcarboxylate into a peptide nucleic acid hexamer. After on-resin conversion of the C5 ester to the 3-(N,N-dimethylamino)propylamide, significant stabilization of the triplex formed with poly(riboadenylic acid) was observed, which illustrates the compatibility of C5 substitution with peptide nucleic acid directed triple helix formation. Key words: peptide nucleic acid, triple helix, orotic acid, orotamide, PNA.

Targeting peptide nucleic acid-protein conjugates to structural features within duplex DNA

1995 ◽  
Vol 3 (4) ◽  
pp. 437-445 ◽  
Author(s):  
James C. Norton ◽  
John H. Waggenspack ◽  
Elana Varnum ◽  
David R. Corey
Keyword(s):  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Structural Features ◽  
Duplex Dna ◽  
Protein Conjugates ◽  
Acid Protein ◽  
Targeting Peptide

scholarly journals Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Felice Amato ◽  
Rossella Tomaiuolo ◽  
Fabrizia Nici ◽  
Nicola Borbone ◽  
Ausilia Elce ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Posttranscriptional Regulation ◽  
Disease Gene ◽  
Md Simulations ◽  
Human Lung Cancer ◽  
Computational Techniques ◽  
Seed Region ◽  
Structural Behaviour

Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its N- and C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3′UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents.

scholarly journals Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a D-lysine-based chiral PNA-DNA duplex

2003 ◽  
Vol 100 (21) ◽  
pp. 12021-12026 ◽  
Author(s):  
V. Menchise ◽  
G. De Simone ◽  
T. Tedeschi ◽  
R. Corradini ◽  
S. Sforza ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Structural Features ◽  
Dna Duplex

High-resolution nucleic acid sequence mapping via in situ hybridization at the Electron Microscope level

1995 ◽  
Vol 53 ◽  
pp. 752-753
Author(s):  
B.A. Hamkalo ◽  
S. Narayanswami ◽  
A.P. Kausch
Keyword(s):  
Nucleic Acid ◽  
Interphase Nucleus ◽  
Genome Mapping ◽  
Precise Location ◽  
Electron Microscope Level ◽  
Rna Sequences ◽  
Fundamental Interest ◽  
Whole Cells ◽  
Dna And Rna

The availability of nonradioactive methods to label nucleic acids an the resultant rapid and greater sensitivity of detection has catapulted the technique of in situ hybridization to become the method of choice to locate of specific DNA and RNA sequences on chromosomes and in whole cells in cytological preparations in many areas of biology. It is being applied to problems of fundamental interest to basic cell and molecular biologists such as the organization of the interphase nucleus in the context of putative functional domains; it is making major contributions to genome mapping efforts; and it is being applied to the analysis of clinical specimens. Although fluorescence detection of nucleic acid hybrids is routinely used, certain questions require greater resolution. For example, very closely linked sequences may not be separable using fluorescence; the precise location of sequences with respect to chromosome structures may be below the resolution of light microscopy(LM); and the relative positions of sequences on very small chromosomes may not be feasible.

Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

2021 ◽  
Vol 23 (1) ◽  
pp. 219-228
Author(s):  
Nabanita Saikia ◽  
Mohamed Taha ◽  
Ravindra Pandey
Keyword(s):  
Nucleic Acid ◽  
Boron Nitride ◽  
Nucleic Acids ◽  
Dynamic Stability ◽  
Peptide Nucleic Acid ◽  
Rational Design ◽  
Peptide Nucleic Acids ◽  
Boron Nitride Nanotubes ◽  
Molecular Hybrids ◽  
Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

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