Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications

2010 ◽  
Vol 7 (3) ◽  
pp. 536-542 ◽  
Author(s):  
Rakesh N. Veedu ◽  
Jesper Wengel
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Therapeutic Applications ◽  
Nucleic Acid Analogs ◽  
Locked Nucleic Acids

scholarly journals Bridged Nucleic Acids Reloaded

2019 ◽  
Author(s):  
Alfonso Soler-Bistué ◽  
Angeles Zorreguieta ◽  
Marcelo E. Tolmasky
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
First Generation ◽  
Second Generation ◽  
Nucleotide Analogs ◽  
Great Hope ◽  
Locked Nucleic Acids ◽  
Near Future

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.

scholarly journals Bridged Nucleic Acids Reloaded

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2297 ◽  
Author(s):  
Alfonso Soler-Bistué ◽  
Angeles Zorreguieta ◽  
Marcelo E. Tolmasky
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
First Generation ◽  
Second Generation ◽  
Nucleotide Analogs ◽  
Great Hope ◽  
Locked Nucleic Acids ◽  
Near Future

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.

Conformationally restricted cationic polyamide analogs of nucleic acids: Design, synthesis, and DNA/RNA binding studies

2004 ◽  
Vol 76 (7-8) ◽  
pp. 1599-1603 ◽  
Author(s):  
V. A. Kumar ◽  
Moneesha D'Costa ◽  
P. S. Lonkar ◽  
P. S. Pallan ◽  
K. N. Ganesh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Water Solubility ◽  
Rna Binding ◽  
Binding Studies ◽  
Design Synthesis ◽  
Conformationally Restricted ◽  
Nucleic Acid Analogs ◽  
Conformational Preferences

The remarkable medicinal importance of the achiral, acyclic, and uncharged aminoethylglycyl peptide nucleic acids (aegPNAs) as DNA/RNA mimics has challenged chemists to circumvent the limitations of their in vivo efficacy. In this context, we have designed conformationally restricted five- and six-membered cyclic PNA analogs by introduction of chemical bridges in aegPNAs leading to a large variety of structures with defined configurations and conformational preferences, effecting concomitant installation of a positive charge in the backbone. The synthesis and biophysical properties of these cationic aminoethylprolyl PNAs, pyrrolidine PNAs, and piperidine PNAs endowed with increased water solubility and affinity toward target nucleic acids is presented. These nucleic acid analogs as lead structures are a part of a chemical evolution process that might give rise to a synthetic nucleic acid analog having optimum properties for medicinal applications.

LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition

1998 ◽  
pp. 455-456 ◽  
Author(s):  
Sanjay K. Singh ◽  
Alexei A. Koshkin ◽  
Jesper Wengel ◽  
Poul Nielsen
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
High Affinity ◽  
Locked Nucleic Acids

LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition

Tetrahedron ◽  
1998 ◽  
Vol 54 (14) ◽  
pp. 3607-3630 ◽  
Author(s):  
Alexei A. Koshkin ◽  
Sanjay K. Singh ◽  
Poul Nielsen ◽  
Vivek K. Rajwanshi ◽  
Ravindra Kumar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Locked Nucleic Acids

ChemInform Abstract: LNA (Locked Nucleic Acids): Synthesis and High-Affinity Nucleic Acid Recognition.

ChemInform ◽  
2010 ◽  
Vol 29 (26) ◽  
pp. no-no
Author(s):  
S. K. SINGH ◽  
P. NIELSEN ◽  
A. A. KOSHKIN ◽  
J. WENGEL
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
High Affinity ◽  
Locked Nucleic Acids

scholarly journals The proto-Nucleic Acid Builder: a software tool for constructing nucleic acid analogs

2020 ◽  
Author(s):  
Asem Alenaizan ◽  
Joshua L Barnett ◽  
Nicholas V Hud ◽  
C David Sherrill ◽  
Anton S Petrov
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rational Design ◽  
Chemical Space ◽  
Software Tool ◽  
Structural Features ◽  
Natural Polymers ◽  
Helical Structures ◽  
Dna And Rna ◽  
Nucleic Acid Analogs

Abstract The helical structures of DNA and RNA were originally revealed by experimental data. Likewise, the development of programs for modeling these natural polymers was guided by known structures. These nucleic acid polymers represent only two members of a potentially vast class of polymers with similar structural features, but that differ from DNA and RNA in the backbone or nucleobases. Xeno nucleic acids (XNAs) incorporate alternative backbones that affect the conformational, chemical, and thermodynamic properties of XNAs. Given the vast chemical space of possible XNAs, computational modeling of alternative nucleic acids can accelerate the search for plausible nucleic acid analogs and guide their rational design. Additionally, a tool for the modeling of nucleic acids could help reveal what nucleic acid polymers may have existed before RNA in the early evolution of life. To aid the development of novel XNA polymers and the search for possible pre-RNA candidates, this article presents the proto-Nucleic Acid Builder (https://github.com/GT-NucleicAcids/pnab), an open-source program for modeling nucleic acid analogs with alternative backbones and nucleobases. The torsion-driven conformation search procedure implemented here predicts structures with good accuracy compared to experimental structures, and correctly demonstrates the correlation between the helical structure and the backbone conformation in DNA and RNA.

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