The reaction of the psoralens with deoxyribonucleic acid

1984 ◽  
Vol 17 (1) ◽  
pp. 1-44 ◽  
Author(s):  
John E. Hearst ◽  
Stephen T. Isaacs ◽  
David Kanne ◽  
Henry Rapoport ◽  
Kenneth Straub
Keyword(s):  
Natural Selection ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Chemical Modification ◽  
Deoxyribonucleic Acid ◽  
Molecular Level ◽  
Virus Particles ◽  
Cross Links ◽  
High Concentrations

Psoralen photochemistry is specific for nucleic acids and is better understood at the molecular level than are all other methods of chemical modification of nucleic acids. These compounds are used both for in vivo structure analysis and for photochemotherapy since they easily penetrate both cells and virus particles. Apparently, natural selection has selected for membrane and virus penetrability during the evolution of these natural products. Most cells are unaffected by relatively high concentrations of psoralens in the absence of ultraviolet light, and the metabolites of the psoralens have thus far not created a problem. Finally, psoralens form both monoadduct and cross-links in nucleic acid helices, the yield of each being easily controlled by the conditions used during the photochemistry.

scholarly journals Barcoding chemical modifications into nucleic acids improves drug stability in vivo

2018 ◽  
Vol 6 (44) ◽  
pp. 7197-7203 ◽  
Author(s):  
Cory D. Sago ◽  
Sujay Kalathoor ◽  
Jordan P. Fitzgerald ◽  
Gwyneth N. Lando ◽  
Naima Djeddar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Drug Stability ◽  
Chemical Modifications

The efficacy of nucleic acid therapies can be limited by unwanted degradation.

Changes in the nucleic acid content of the uterus of sheep during involution following ovariectomy and following oestrogenic stimulation

1976 ◽  
Vol 27 (5) ◽  
pp. 669 ◽  
Author(s):  
DA Little ◽  
LJ Lambourne
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Ribonucleic Acid ◽  
Acid Content ◽  
Deoxyribonucleic Acid ◽  
Total Content ◽  
Mean Value ◽  
Nucleic Acid Content ◽  
Uterine Tissue ◽  
Rna Concentration

The concentrations of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), in ovine uterine tissue were studied to determine whether the ratio RNA/DNA might be used in the bioassay of oestrogenic activity. As the uterus decreased in size with time after ovariectomy, the concentration of DNA increased markedly, but the total content of DNA in the uterus remained constant (mean value 342 ? 8 (SE) mg). The RNA concentration of the tissue decreased during involution, with the result that a highly significant reduction of 33% in the RNA/DNA ratio occurred within 2 weeks of ovariectomy. The ratio decreased further with time. Other ewes were treated for 3 days with diethylstilboestrol dipropionate (10 µg/day), commencing 2 weeks after ovariectomy; the stage of the oestrous cycle at which the ovaries were removed had no effect on the response to the oestrogen. Changes in the nucleic acid concentrations in the uteri of these ewes, and the results obtained during involution, indicate that the RNA/DNA ratio of uterine tissue in ovariectomized ewes has potential as a basis for the bioassay of materials of low oestrogenic potency.

scholarly journals Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4659 ◽  
Author(s):  
Steven Ochoa ◽  
Valeria T. Milam
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Chemical Structure ◽  
Chemical Diversity ◽  
Physiochemical Properties ◽  
Phosphate Backbone ◽  
Modified Nucleic Acids ◽  
Recent Developments ◽  
Diagnostic Applications

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.

Hydroxyproline-Based DNA Mimics: A Review on Synthesis and Properties

2006 ◽  
Vol 71 (7) ◽  
pp. 929-955 ◽  
Author(s):  
Vladimir A. Efimov ◽  
Oksana G. Chakhmakhcheva
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Phosphonic Acid ◽  
Peptide Nucleic Acids ◽  
Biological Properties ◽  
High Potential ◽  
Physicochemical And Biological Properties

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.

scholarly journals Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids

2020 ◽  
Vol 21 (6) ◽  
pp. 2001
Author(s):  
Silvia Mercurio ◽  
Silvia Cauteruccio ◽  
Raoul Manenti ◽  
Simona Candiani ◽  
Giorgio Scarì ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Neural Development ◽  
Peptide Nucleic Acids ◽  
Model Organism ◽  
Ciona Intestinalis ◽  
Transcriptional Level ◽  
Regulate Gene Expression

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

Clinical Trials of Functional Nucleic Acids

2018 ◽  
Vol 7 (2) ◽  
pp. 46-60 ◽  
Author(s):  
Martina Traykovska ◽  
Sjoerd Miedema ◽  
Robert Penchovsky
Keyword(s):  
Clinical Trials ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Pharmaceutical Companies ◽  
Nucleic Acid Therapeutics ◽  
Drug Candidates ◽  
Safety Risks ◽  
Functional Nucleic Acids ◽  
Administration Methods

This chapter describes how functional nucleic acids, such as aptamers, antisense oligonucleotides (ASOs), small interfering (si) RNAs, and ribozymes are considered by some researchers as valuable tools to develop therapeutic agents. They have not been particularly fast in reaching the market as medicines, due to endogenous barriers to extracellular trafficking and cellular uptake of nucleic acids and their inherent instability when applied in vivo. However, research carried out by the nucleic acid engineering community and pharmaceutical companies to circumvent these obstacles has led to the approval of a few aptamers and ASOs as drugs. Nucleic acid therapeutics are usually administered locally to diseased tissue. The drug candidates currently in clinical trials commonly use the same administration methods as previously licensed nucleic acid therapeutics. These administration techniques carry their own safety risks and advantages. In this article, the present state is discussed and prospective options for the use ASOs and aptamers as drugs are listed.

scholarly journals THE INCORPORATION OF FORMATE-C14 INTO THE NUCLEIC ACIDS OF RATS WITH REGENERATING LIVER AND NOVIKOFF HEPATOMA

1959 ◽  
Vol 37 (1) ◽  
pp. 1405-1416 ◽  
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Mitotic Activity ◽  
Intestinal Mucosa ◽  
Regenerating Liver ◽  
Simultaneous Presence ◽  
Novikoff Hepatoma ◽  
Mitotic Frequency ◽  
Host Tissues

A study was made of the incorporation in vivo of formate-C14 into the purines and thymine of regenerating liver and Novikoff hepatoma in the rat, during the period of maximum mitotic activity of these tissues. The effects of these tissues on one another and on certain host tissues were also studied. The maximum mitotic frequency of Novikoff hepatoma was observed on the 4th day of growth following transplantation. This tumor caused a decrease in formate incorporation into the nucleic acid purines and thymine of the host's spleen and intestinal mucosa but had little effect on liver. The results also indicated that the uptake of formate by the RNA adenine of spleen and intestinal mucosa and the DNA thymine of intestinal mucosa was diminished by the presence of regenerating liver. The simultaneous presence of both regenerating liver and Novikoff hepatoma generally lowered the incorporation of formate-C14 into the nucleic acids of the host spleen and intestinal mucosa. It was observed further that the utilization of formate by the nucleic acids of Novikoff hepatoma and regenerating rat liver was decreased in animals containing both of these rapidly dividing tissues.

Nucleic Acids in Grass and Grass Silage

1988 ◽  
Vol 1988 ◽  
pp. 86-86
Author(s):  
A B McAllan ◽  
G D Braithwaite
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Protein Content ◽  
Ribonucleic Acid ◽  
Protein Fraction ◽  
Dry Matter ◽  
Deoxyribonucleic Acid ◽  
Total N ◽  
Grass Silage ◽  
Microbial N

Little attention has been directed at defining the ‘protein’ fraction of silages. This component is normally estimated by fractionation based on solubility characteristics and under the conditions most commonly used, nucleic acids (ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)) would appear in the protein fraction. Grasses and legumes can contain appreciable amounts of nucleic acids ranging from 11-29 and 19-53 g/kg dry matter respectively (McAllan, 1982). No information is available as to the effects of ensilage on these nucleic acids. Microbes also contain appreciable amounts of nucleic acids which can account for 150-200 gN/kg total-N of the cell and these amounts may vary according to the stage of growth. It has been suggested (Ullrich, 1982) that microbial-N contribution to the total-N content of silage is as much as 220-280 g/kg. Thus the total amount of silage ‘protein-N’ present in the form of nucleic acid-N (from both plant and microbes) could be appreciable leading to a considerable overestimation of the ‘protein’ content of the silage.

scholarly journals Enrichment of Zα domains at cytoplasmic stress granules is due to their innate ability to bind nucleic acids

2021 ◽  
Author(s):  
Luisa Gabriel ◽  
Bharath Srinivasan ◽  
Krzysztof Kuś ◽  
João F. Mata ◽  
Maria João Amorim ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Stress Granules ◽  
Helical Conformation ◽  
Nucleic Acid Binding ◽  
Mobility Shift ◽  
Binding Ability ◽  
Amino Terminal ◽  
Mobility Shift Assay

Zα domains recognize the left-handed helical conformation of double stranded nucleic acids. They are found in proteins involved in the nucleic acid sensory pathway of vertebrate innate immune system and host evasion by viral pathogens. Previously, it has been demonstrated that ADAR1 and DAI localize to the cytosolic stress granules mediated by their Zα domains. To investigate the mechanism, we determined the interactions and localization pattern for the amino-terminal region of human DAI harbouring two Zα domains (ZαβDAI) and a nucleic acid-binding deficient mutant. Electrophoretic mobility shift assay demonstrated the ability of ZαβDAI to bind to hyperedited nucleic acids which are enriched in stress granules. Further, using immunofluorescence and immunoprecipitation coupled with mass-spectrometry, we identified several interacting partners of the ZαβDAI-RNA complex in-vivo under conditions of arsenite-induced stress. These interactions are lost upon loss of nucleic acid binding ability or with RNase treatment. Thus, we posit that the mechanism for the translocation of Zα domain-containing proteins to stress granules is mainly mediated by the nucleic acid binding ability of their Zα domains.

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