scholarly journals Bridged Nucleic Acids Reloaded

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2297 ◽  
Author(s):  
Alfonso Soler-Bistué ◽  
Angeles Zorreguieta ◽  
Marcelo E. Tolmasky

Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs that, when part of these oligomers, enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs is the first-generation bridged nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second-generation BNA, BNANC (2′-O,4′-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but, in some cases, also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds have been researched, the promising results warrant more effort in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future, offering great hope to oligonucleotide-based fields of research and applications.

Author(s):  
Alfonso Soler-Bistué ◽  
Angeles Zorreguieta ◽  
Marcelo E. Tolmasky

Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, led to the design of nucleotide analogs that when being part of these oligomers enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs are the first-generation bridge nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second generation BNA, BNANC (2'-O,4'-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but in some cases also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds were researched, the results are very promising warranting more efforts in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future offering great hope to oligonucleotide-based fields of research and applications.


2002 ◽  
Vol 48 (8) ◽  
pp. 1186-1193 ◽  
Author(s):  
Philip J Johnson ◽  
YM Dennis Lo

Abstract Background: There is a need for development of molecular markers of cancer that can be used clinically for the detection, prognostication, and monitoring of cancer. Recently, there has been much interest in the potential use of nucleic acid markers in plasma and serum for this purpose. Approach: We reviewed published literature up to 2002 on the topic, with a particular emphasis on reports published between 1996 and 2002. Content: The nucleic acid markers described in plasma and serum include oncogene mutations/amplifications, microsatellite alterations, and gene rearrangements. Such markers have been described in many cancer types, including lung, colon, and breast. Epigenetic alterations, such as aberrant promoter methylation, have been identified in plasma and serum. Viral nucleic acid markers, such as Epstein–Barr virus DNA in plasma and serum, are reviewed in detail with regard to their application to virus-associated cancers such as nasopharyngeal carcinoma and various lymphomas. More recently, mitochondrial DNA and tumor-related mRNAs have been identified in plasma and serum from patients with several types of tumors. Conclusions: Circulating nucleic acids are an emerging class of molecular tumor markers. Their wide applicability and clinical relationship with the malignant state will likely grant them increasing clinical importance in the near future.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Yuuya Kasahara ◽  
Masayasu Kuwahara

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.


1928 ◽  
Vol 47 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Julius A. Klosterman ◽  
Kathryn W. Small

Of the attempts to isolate an antidiphtheria phage (1) from stools collected daily during the course of a case of the disease, (2) from a 33 day old broth culture of B. diphtheriæ, (3) from intestinal contents and peritoneal washings of guinea pigs inoculated with three different toxic strains of B. diphtheriæ, none yielded an antidiphtheria phage. However of eleven specimens of feces collected from eleven antitoxin horses one was found to contain a bacteriophage active against B. diphtheriæ. This phage was not observed in the first generation and did not show up until transferred the second time. Had the results of the first transfer been regarded as final in all certainty the existence of a phage would not have been recognized. Two additional specimens of feces from the positive horse (No. 156) were later tested to determine whether this bacteriophage was continually present in the intestinal tract of this animal. Both of these feces filtrates failed to yield a phage. Later a sample of freshly collected blood serum from the same horse was tested and found not to contain a phage. The antidiphtheria phage was tested against eighteen non-diphtheria strains of microorganisms to determine whether it would show lytic activity for related or unrelated bacteria. There was no evidence of lysis in any of these types. The specificity of this phage was also tested on nine strains of B. diphtheriæ and found to be active on three heterologous strains (Strain M 1314, Strain F and Strain G). These incidentally were all recently isolated. It failed to lyse the remaining six strains of which five were recently isolated. B. diphtheriæ Strain M 1314 was used in combination with nine heterologous bacteriophages isolated from various sources, to determine if any of these phages would by chance lyse this culture. The results were all negative. To date this phage fails to show complete lysis although the twenty-second generation has a titer of 1 x 10–9. Additional proposed experiments involving this phage are being planned and will be undertaken in the near future.


2013 ◽  
Vol 69 (11) ◽  
pp. 2174-2185 ◽  
Author(s):  
Marco Marcia ◽  
Elisabeth Humphris-Narayanan ◽  
Kevin S. Keating ◽  
Srinivas Somarowthu ◽  
Kanagalaghatta Rajashankar ◽  
...  

Structured RNA molecules are key players in ensuring cellular viability. It is now emerging that, like proteins, the functions of many nucleic acids are dictated by their tertiary folds. At the same time, the number of known crystal structures of nucleic acids is also increasing rapidly. In this context, molecular replacement will become an increasingly useful technique for phasing nucleic acid crystallographic data in the near future. Here, strategies to select, create and refine molecular-replacement search models for nucleic acids are discussed. Using examples taken primarily from research on group II introns, it is shown that nucleic acids are amenable to different and potentially more flexible and sophisticated molecular-replacement searches than proteins. These observations specifically aim to encourage future crystallographic studies on the newly discovered repertoire of noncoding transcripts.


2013 ◽  
Vol 78 (19) ◽  
pp. 9560-9570 ◽  
Author(s):  
Sujay P. Sau ◽  
Andreas S. Madsen ◽  
Peter Podbevsek ◽  
Nicolai K. Andersen ◽  
T. Santhosh Kumar ◽  
...  

1998 ◽  
pp. 455-456 ◽  
Author(s):  
Sanjay K. Singh ◽  
Alexei A. Koshkin ◽  
Jesper Wengel ◽  
Poul Nielsen

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