Acyclic oligonucleotides: possibilities and limitations

Vandendriessche, F.; Augustyns, Koen; Aerschot, Arthur Van; Busson, Roger; Hoogmartens, Jos; Herdewijn, Piet

doi:10.1016/s0040-4020(01)87200-8

Cited by 50 publications

(24 citation statements)

References 25 publications

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“…In addition, incorporation of acyclic moieties into DNA often caused destabilization of the duplex. Structural discordance between natural DNA and these analogues might be the reason for the instability 30–34…”

Section: Discussionmentioning

confidence: 99%

Highly Stable Duplex Formation by Artificial Nucleic Acids Acyclic Threoninol Nucleic Acid (aTNA) and Serinol Nucleic Acid (SNA) with Acyclic Scaffolds

Murayama

Tanaka

Toda

et al. 2013

Chemistry A European J

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The stabilities of duplexes formed by strands of novel artificial nucleic acids composed of acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA) building blocks were compared with duplexes formed by the acyclic glycol nucleic acid (GNA), peptide nucleic acid (PNA), and native DNA and RNA. All acyclic nucleic acid homoduplexes examined in this study had significantly higher thermal stability than DNA and RNA duplexes. Melting temperatures of homoduplexes were in the order of aTNA>PNA≈GNA≥SNA≫RNA>DNA. Thermodynamic analyses revealed that high stabilities of duplexes formed by aTNA and SNA were due to large enthalpy changes upon formation of duplexes compared with DNA and RNA duplexes. The higher stability of the aTNA homoduplex than the SNA duplex was attributed to the less flexible backbone due to the methyl group of D-threoninol on aTNA, which induced clockwise winding. Unlike aTNA, the more flexible SNA was able to cross-hybridize with RNA and DNA. Similarly, the SNA/PNA heteroduplex was more stable than the aTNA/PNA duplex. A 15-mer SNA/RNA was more stable than an RNA/DNA duplex of the same sequence.

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Section: Discussionmentioning

confidence: 99%

Highly Stable Duplex Formation by Artificial Nucleic Acids Acyclic Threoninol Nucleic Acid (aTNA) and Serinol Nucleic Acid (SNA) with Acyclic Scaffolds

Murayama

Tanaka

Toda

et al. 2013

Chemistry A European J

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“…This flexibility could allow the base of the analogue to position itself and allow perfect base-pairing with all four natural base moieties. Our previous findings already indicated the acyclic hypoxanthine analogue 1 to be a good candidate as a universal base: only a small spread in Tm versus the complementary sequences was noticed when incorporated at a degenerate position (4). However, the slight destabilisation ofthe duplex (a drop in Tm of 5°C compared with incorporation of the normal Watson-Crick base pairs) led us to look for a base analogue which would yield analogous ambiguous pairing with all four natural bases as the counterpart, but without a drop in melting temperature.…”

Section: Introductionmentioning

confidence: 93%

An acyclic 5-nitroindazole nucleoside analogue as ambiguous nucleoside

Rozenski¹,

Loakes

Pillet³

et al. 1995

Nucl Acids Res

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Acyclic nucleoside analogues with carboxamido-or nitro-substituted heterocyclic bases have been evaluated for their possible use as universal bases in oligodeoxynucleotides. The acyclic moiety endows the constructs with enough flexibility to allow good base stacking. The 5-nitroindazole analogue afforded the most stable duplexes among the acyclic derivatives with the least spread in Tm versus the four natural bases. In spite of the acyclic moiety, stabilities are comparable with those of duplexes incorporating the recently described 5-nitroindole nucleoside analogue, but considerably exceed those for the 3-nitropyrrole analogue.

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“…For instance, the acyclo or 'seco'-nucleotides are much simpler to synthesize and easily cease the progression of 3'-exonucleolytic digestion to exhibit excellent in vitro stabilities with half-lives of greater than 19 h reported in cell culture (i.e. 2% oligo degraded) [127]. Secondly, the lipophilic character of the residues can easily be adjusted to promote unimpeded entry of the oligonucleotide into the cellular space.…”

Section: Acyclonucleotides: Biological Effects Of Monomer Conformatiomentioning

confidence: 99%

Flexible and Frozen Sugar-Modified Nucleic Acids - Modulation of Biological Activity Through Furanose Ring Dynamics in the Antisense Strand

Mangos¹,

Damha

2002

CTMC

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A comparison of carbohydrate modified nucleic acids has identified key structural characteristics in antisense oligonucleotides (AON) that are necessary for sufficient clinical utility, including increased duplex stability towards RNA complements and improved hydrolytic resistance towards general serum and cellular nucleases. As such, the exogenous addition of short, synthetic oligonucleotides can influence cellular RNA metabolism at any or all levels of replication, transcription or translation by tight and specific hybridization with a chosen target and subsequently stop further function at that site. Furthermore, appropriate modification of the sugar residue may prove to be a vital design element in future AONs that operate by promoting enzyme assisted catalytic destruction of the mRNA target. Unfortunately, many of the current AON designs have provided little insight on the particular structural role of the AON towards enzymatic discrimination of the resultant hybrid. The use of RNase H as a cellular vehicle to assist the inhibitory potency of an AON as well as possible ways of enhancing activity in pre-existing antisense candidates are presented. Of the emerging criteria in this aspect, a balance between flexibility and rigidity within the AON appears to be a critical mediator of the RNase H assisted antisense effect. Accordingly, this review describes the conformational features and selected biological attributes of some of the more prominent AON contenders with a focus on the conformational criteria by which ribonuclease H activity is recruited to a particular hybrid target.

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Acyclic oligonucleotides: possibilities and limitations

Cited by 50 publications

References 25 publications

Highly Stable Duplex Formation by Artificial Nucleic Acids Acyclic Threoninol Nucleic Acid (aTNA) and Serinol Nucleic Acid (SNA) with Acyclic Scaffolds

Highly Stable Duplex Formation by Artificial Nucleic Acids Acyclic Threoninol Nucleic Acid (aTNA) and Serinol Nucleic Acid (SNA) with Acyclic Scaffolds

An acyclic 5-nitroindazole nucleoside analogue as ambiguous nucleoside

Flexible and Frozen Sugar-Modified Nucleic Acids - Modulation of Biological Activity Through Furanose Ring Dynamics in the Antisense Strand

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