2'-Deoxy-2'-fluoro-beta-D-arabinonucleosides and oligonucleotides (2'F-ANA): synthesis and physicochemical studies

Wilds, Christopher J.; Damha, Masad J.

doi:10.1093/nar/28.18.3625

Cited by 156 publications

(194 citation statements)

References 38 publications

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“…The synthesis of the 1-[2-deoxy-2-fluoro-5-O-(4,4′-dimethoxytrityl)-3-O-( -cyanoethyl-N,N-diisopropylphosphoramidite)--D-arabinofuranosyl] thymine monomer was previously described (13)…”

Section: Methodsmentioning

confidence: 99%

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2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Sarkhel

Wilds

et al. 2006

Biochemistry

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2′-Deoxy-2′-fluoro-arabinonucleic acid (FANA) and arabinonucleic acid (ANA) paired to RNA are substrates of RNase H. The conformation of the natural DNA/RNA hybrid substrates appears to be neither A-form nor B-form. Consistent with this, the conformations of FANA and ANA were found to be intermediate between the A-and B-forms. However, FANA opposite RNA is preferred by RNase H over ANA, and the RNA affinity of FANA considerably exceeds that of ANA. By investigating the conformational boundaries of FANA and ANA residues in crystal structures of A-and B-form DNA duplexes at atomic resolution, we demonstrate that FANA and ANA display subtle conformational differences. The structural data provide insight into the structural requirements at the catalytic site of RNase H. They also allow conclusions with regard to the relative importance of stereoelectronic effects and hydration as modulators of RNA affinity.

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“…The synthesis of the 1-[2-deoxy-2-fluoro-5-O-(4,4′-dimethoxytrityl)-3-O-( -cyanoethyl-N,N-diisopropylphosphoramidite)--D-arabinofuranosyl] thymine monomer was previously described (13)…”

Section: Methodsmentioning

confidence: 99%

“…CD-spectra of DNA/RNA, FANA/RNA, and ANA/RNA duplexes in solution, although displaying close similarity, show distinct positive bands near 270 nm (13). Both X-ray crystallography and NMR solution studies indicated the O4′-endo (East (18)) conformation as preferred by FANA sugars (19,20).…”

mentioning

confidence: 95%

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Sarkhel

Wilds

et al. 2006

Biochemistry

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“…In the crystallographic model, the carbonyl group of the amide moiety faces the minor groove, and the methyl substituent is directed away from the duplex ( Figure 5). The structure allows no firm conclusions regarding a potential role of the solvent in the stability increases as a result of the amide modification because the current model includes only a limited number of water molecules (17). It is possible that an R-configuration of the methyl substituent (modification III) would lead to closer contacts between the methyl group and the sugar moiety of the 5′-T ( Figure 5).…”

Section: ′-Cgcaaaaaaaaaacgc-3′ (Complementary To B)mentioning

confidence: 97%

RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures^,

et al. 2006

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Among the hundreds of nucleic acid analogues that have been studied over the last two decades only very few exhibit backbones with linkers between residues that are either shorter or longer than the four-atom linker O3′-P-O5′-C5′ connecting sugar ring moieties in DNA and RNA. 2′-Deoxyribonucleoside dimers connected by a five-atom linker O3′-CH*(CH 3 )-CO-NH-CH 2 (* designates a chiral center) were reported to lead to only a slight destabilization of RNA-DNA hybrids in which the DNA strand contained one or several of these amide-linked dimers (De Napoli, L., Iadonisi, A., Montesarchio, D., Varra, M., and Piccialli, G. (1995) Synthesis of thymidine dimers containing a new internucleosidic amide linkage and their incorporation into oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett. 5, 1647Lett. 5, -1652. To analyze the influence of various chemistries of such five-atom amide linkers on the RNA-binding affinity of modified DNA strands, we have synthesized five different amide-linked dimers, including structures with homochiral linkers of the type X3′-C*H(CH 3 )-CO-NH-CH 2 (X ) O, CH 2 ) as well as the corresponding analogues carrying methoxy groups at the 2′-position of the 3′-nucleosides. We have conducted a detailed thermodynamic analysis of duplex formation between the modified DNA and RNA, with the DNA strands containing between one and seven consecutive modified dimers. Some of the five-atom-linked dimers lead to significantly higher RNA-binding affinities compared with that of native DNA. Interestingly, the linkers with opposite stereochemistry at the chiral center stabilize duplexes between the modified DNA and RNA to different degrees. CD spectroscopy in solution and a crystal structure of an RNA-DNA duplex with a single amide-linked dimer demonstrate that the longer amide backbones do not disrupt the duplex geometry. These observations provide further evidence that stable cross-pairing between two different types of nucleic acids does not require the numbers of atoms linking their individual residues to match.

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“…Some of the most prominent examples are 2 0 -fluoro (2 0 -F), 107,108 2 0 -O-methyl (2 0 -OMe), 109 2 0 -methoxyethyl (2 0 -MOE), 110,111 2 0 -fluoroarabino (2 0 -FANA), 112 locked nucleic acid (LNA), 113,114 unlocked nucleic acid (UNA), 115,116 cyclohexenyl (CeNA) nucleic acid, 117,118 peptide nucleic acid (PNA), 119 phosphoramidate morpholino (PMO) 120 etc. Although many of the modified nucleotides have been successfully utilized in various nucleic acid-based therapeutic technologies, their relatively poor or no enzymatic recognition properties often pose a major challenge toward the development of biostable aptamers.…”

Section: Chemically Modified Aptamer-oligonucleotide Chimeramentioning

confidence: 99%

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

et al. 2015

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2'-Deoxy-2'-fluoro-beta-D-arabinonucleosides and oligonucleotides (2'F-ANA): synthesis and physicochemical studies

Cited by 156 publications

References 38 publications

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures^,

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

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2'-Deoxy-2'-fluoro-beta-D-arabinonucleosides and oligonucleotides (2'F-ANA): synthesis and physicochemical studies

Cited by 156 publications

References 38 publications

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H,

RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures,

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Contact Info

Product

Resources

About

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures^,