An Approach to Chemotherapy Based on Base Sequence Information and Nucleic Acid Chemistry Matagen (Masking Tape for Gene Expression)

Ts’o, Paul O. P.; Miller, Paul S.; Aurelian, Laure; Murakami, Akira; Agris, Cheryl H.; Blake, Kathleen R.; Lin, Shwu‐Bin; Lee, Bok L.; Smith, Cynthia C.

doi:10.1111/j.1749-6632.1987.tb45804.x

Cited by 40 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is largely an enthalpic effect which becomes a destabilizing factor in the final complex (depending, of course, on ionic strength) . A number of molecular strategies for lowering this repulsion in DNA have been realized in recent years; for example, an oligonucleotide could be modified to carry an uncharged , or even a positively charged backbone, , thus leading to lowered or eliminated electrostatic repulsion or even attraction between the oligonucleotide and its target. While not an entropic preorganization strategy, it can be useful for enhancing binding, especially at low ionic strength.…”

Section: Electrostatic Effectsmentioning

confidence: 99%

“…Two separate molecules can act as ligands for one molecule without even contacting each other, and still do so with a measure of cooperativity in certain instances. For example, a sequence of C,T-containing peptide nucleic acid will not bind a purine complementary sequence of DNA by formation of a duplex, but will instead proceed to form a three-stranded complex in which two PNA strands clamp the target DNA (Figure ) …”

Section: Triplex Formation On Single-stranded Targetsmentioning

confidence: 99%

See 1 more Smart Citation

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

1997

View full text Add to dashboard Cite

Section: Electrostatic Effectsmentioning

confidence: 99%

Section: Triplex Formation On Single-stranded Targetsmentioning

confidence: 99%

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

1997

View full text Add to dashboard Cite

“…In general, nucleic acid analogs should a) have higher affinity per nucleotide unit than the cognate sequence, without changing the structure of duplexes, b) be resistant to nucleases, and c) have low toxicity. The first oligonucleotide analogs consisted of relatively minor modifications to the natural counterparts, such as the replacement of an oxygen atom by sulfur (phosphorothioate) [15,16], methyl (methylphosphonate) [17], or amino groups (phosphoramidate) (Figure 1). The value of using nucleotide analogs was illustrated by the first FDA approved antisense drug, fomivirsen, a 21-nucleotide oligomer composed of phosphorothioate units designed for the treatment of cytomegalovirus retinitis [10,18].…”

Section: Oligonucleotides and Analogsmentioning

confidence: 99%

Bridged Nucleic Acids Reloaded

2019

View full text Add to dashboard Cite

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.

show abstract

“…TACTTTACTGATAAC-lipid, 32 TTCTTTACTGALTA2TC-lipid, 13 controls TCTAATCCAAGAGAC-lipid, 14 (randomized 9) AACTTAACCATCGAG, 15 (randomLized 7) TCTAATCCAAGAGAC, 16 (thioate, randomized 8) TTTTTTTTTTTTTTT-lipid, 17 Fig. 5.…”

Section: ' ---Acatatgaaaaaactaacagatatca-ggataatctcacaaaagtt---3'mentioning

confidence: 99%

Synthesis, hybridization properties and antiviral activity of lipid-oligodeoxynucleotide conjugates

Shea¹,

Marsters²,

Bischofberger³

1990

Nucl Acids Res

148

View full text Add to dashboard Cite

Triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (2) was coupled to the 5' terminus of oligodeoxynucleotides via hydrogen phosphonate solid support DNA synthesis methodology. Duplex DNA oligomers with a single 5'-phospholipid melted at lower temperatures than the corresponding unmodified duplex, but duplexes bearing lipids at each 5' end had higher Tms. In uptake experiments with L929 cells, 8-10 times more lipid-DNA became cell-associated than did unmodified DNA. Unmodified antisense diesters were inactive in a VSV antiviral assay in L929 cells (at up to 200 microM). Attachment of a lipid to the oligomer, however, led to a greater than 90% at 150 microM (greater than 80% at 100 microM) reduction in viral protein synthesis. The antiviral activity depended on the sequence of the oligodeoxynucleotide, but some compounds having little or no base complementarity to the viral target were also effective. Phosphorothioate derivatives reduced viral protein synthesis by 20-30% at 100 microM in the VSV assay. The lipid-DNA compounds were not toxic to the cells at up to 100 microM.

show abstract

An Approach to Chemotherapy Based on Base Sequence Information and Nucleic Acid Chemistry Matagen (Masking Tape for Gene Expression)

Cited by 40 publications

References 13 publications

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

Bridged Nucleic Acids Reloaded

Synthesis, hybridization properties and antiviral activity of lipid-oligodeoxynucleotide conjugates

Contact Info

Product

Resources

About