Polyaminooligonucleotide: NMR structure of duplex DNA containing a nucleoside with spermine residue, N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine

Brzezinska, Jolanta; Gdaniec, Zofia; Popenda, Łukasz; Markiewicz, Wojciech T.

doi:10.1016/j.bbagen.2013.12.008

Cited by 16 publications

(20 citation statements)

References 55 publications

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“…Markiewicz et al and Brzezinska et al observed increases in DNA duplex stability of 4°C per modification upon introduction of C-4 spermine-modified dU into an octamer ODN [88,99]. In contrast, Prakash et al described a decrease in ODN-DNA duplex stability on incorporation of an internally positioned C-4-modified dT in the ODN [89].…”

Section: Base-modified Polyamine-oligonucleotide Conjugatesmentioning

confidence: 87%

“…These inconsistencies might be explained by differing experimental conditions (e.g., Mg 2+ concentration) in the melting temperature experiments, or the presence of a C-5 methyl group in Prakash's modified nucleoside. A recent NMR structure of an octamer ODN-DNA duplex containing a spermine-modified dC (structure 32) shed light on the interactions between the bound spermine and the oligonucleotide duplex structure (Figure 2) [88]. The authors found that the appended spermine lies in the major groove of the B-form helix, similar to that observed for aminopropyl-modifications of C-5 of dU, and is oriented itself towards the 3´ end of the modified strand with a loose alignment to the phosphate backbone ( Figure 2A) [75].…”

Section: Base-modified Polyamine-oligonucleotide Conjugatesmentioning

confidence: 99%

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Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

2015

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Chemical modification and/or the conjugation of small functional molecules to oligonucleotides have significantly improved their biological and biophysical properties, addressing issues such as poor cell penetration, stability to nucleases and low affinity for their targets. Here, the authors review the literature reporting on the biophysical, biochemical and biological properties of one particular class of modification - polyamine-oligonucleotide conjugates. Naturally derived and synthetic polyamines have been grafted onto a variety of oligonucleotide formats, including antisense oligonucleotides and siRNAs. In many cases this has had beneficial effects on their properties such as target hybridization, nuclease resistance, cellular uptake and activity. Polyamine-oligonucleotide conjugation, therefore, represents a promising direction for the further development of oligonucleotide-based therapeutics and tools.

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Section: Base-modified Polyamine-oligonucleotide Conjugatesmentioning

confidence: 87%

Section: Base-modified Polyamine-oligonucleotide Conjugatesmentioning

confidence: 99%

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

2015

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“…It was shown previously that polyamine conjugation to oligodeoxyribonucleotides results in stabilizing of DNA duplexes and triplexes [2][3][4]38,39,[41][42][43]. Recently, we described the NMR structure of a DNA duplex carrying a single spermine modified deoxycytidine unit [34]. This modification moderately stabilizes the DNA duplex ( Figure 3, dC Sp vs. RF1) and does not perturb the DNA structure.…”

Section: Stability Of Duplexes With Modified Oligodeoxyribonucleotidesmentioning

confidence: 99%

“…This modification moderately stabilizes the DNA duplex ( Figure 3, dC Sp vs. RF1) and does not perturb the DNA structure. [34]; ON3, ON7-non-nucleosidic putrescine analogues (Table 2); ON4-ON6 and ON8-ON9-non-nucleosidic spermine analogues ( Table 2). …”

Section: Stability Of Duplexes With Modified Oligodeoxyribonucleotidesmentioning

confidence: 99%

“…There have been numerous studies aimed at determining these interactions using NMR imaging, circular dichroism, Raman spectroscopy, IR spectroscopy, X-ray crystallography and differential scanning calorimetry. In spite of these extensive studies, precise mechanisms for the interaction between polyamine and DNA is still not fully understood in vivo [34].…”

Section: Introductionmentioning

confidence: 99%

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Non-Nucleosidic Analogues of Polyaminonucleosides and Their Influence on Thermodynamic Properties of Derived Oligonucleotides

Brzezinska

Markiewicz

2015

Molecules

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Abstract:The rationale for the synthesis of cationic modified nucleosides is higher expected nuclease resistance and potentially better cellular uptake due to an overall reduced negative charge based on internal charge compensation. Due to the ideal distance between cationic groups, polyamines are perfect counterions for oligodeoxyribonucleotides. We have synthesized non-nucleosidic analogues built from units that carry different diol structures instead of sugar residues and functionalized with polyamines. The non-nucleosidic analogues were attached as internal or 5′-terminal modifications in oligodeoxyribonucleotide strands. The thermodynamic studies of these polyaminooligonucleotide analogues revealed stabilizing or destabilizing effects that depend on the linker or polyamine used.

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Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding Kinetics

Menzi

Wild

Pradère

et al. 2017

Chemistry A European J

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When used as inhibitors of gene expression in vivo, oligonucleotides require modification of their structures to boost their binding affinity for complementary target RNAs. To date, hundreds of modifications have been designed and tested but few have proven to be useful. Among those investigated are mono- and polyamino-groups. These are positively charged at physiological pH and have been appended to oligonucleotides in an effort to reduce electrostatic repulsion during hybridization to RNAs, but have generally shown relatively minor benefits to binding. We conjugated spermine to uracils in oligonucleotides via a triazole linker so that the polyamine fits in the major groove of a subsequently formed RNA-duplex. The modifications produced large increases in target-binding affinity of the oligonucleotides. Using surface plasmon resonance-based assays, we showed that the increases derived mainly from faster annealing (k ). We propose that the spermine fragments play a similar role to that of natural polyamines during oligonucleotide-target interactions in cells, and may be advantageous for oligonucleotides that operate catalytic mechanisms.

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Polyaminooligonucleotide: NMR structure of duplex DNA containing a nucleoside with spermine residue, N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine

Cited by 16 publications

References 55 publications

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

Non-Nucleosidic Analogues of Polyaminonucleosides and Their Influence on Thermodynamic Properties of Derived Oligonucleotides

Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding Kinetics

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