Syntheses and Interactions of Oligodeoxyribonucleotides Containing 2′-Amino-2′-Deoxyuridine

Miller, Paul S.; Bhan, Purshotam; Kan, Lou Sing

doi:10.1080/07328319308018549

Cited by 24 publications

(22 citation statements)

References 18 publications

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“…These expectations could not be observed in the presented investigations, since we found in all cases of hybridizations decreased T, values due to destabilizing effects resulting probably from electrostatic interactions between the 2'-amino and the negatively charged phosphodiester function, and unknown secondary effects perturbing a normal duplex structure as also described by Shaharova and co-workers [24], Miller et al [49], and Eckstein and co-workers [50].…”

contrasting

confidence: 68%

Nucleotides. Part LVII.. Synthesis of phosphoramidite building blocks of 2′‐amino‐2′‐deoxyribonucleosides: New compounds for oligonucleotide synthesis

Greiner¹,

Pfleiderer²

1998

Helvetica Chimica Acta

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The chemical synthesis of 2'-amino-2'-deoxyribonucleosides of uracil, cytosine. adenine, and guanine, and their conversion into suitably protected 3'-phosphoramidite building blocks 35-40 for oligonucleotide synthesis are described. The aglycone and the 2'-amino functions were protected using the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group. The synthesis of the 3'-U-succinyl (3'-U-(3-carboxypropanoyl))-substituted starting nucleoside 41 is described and its behavior examined in solution and on solid phase with regard to an anticipated migration during 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) deprotection. Oligonucleotides were prepared using the new building blocks, and their hybridization properties were studied by UV-melting techniques.

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confidence: 68%

Nucleotides. Part LVII.. Synthesis of phosphoramidite building blocks of 2′‐amino‐2′‐deoxyribonucleosides: New compounds for oligonucleotide synthesis

Greiner¹,

Pfleiderer²

1998

Helvetica Chimica Acta

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“…In model duplexes, a single 2Ј-NH 2 substitution has been observed to cause profound destabilization of the helix (35,36), while 2Ј-F-or 2Ј-OMe-modified oligomers generally show enhanced helix stabilities (32,37,59). The VEGF aptamers derived from 2Ј-Fpyrimidine-modified RNA libraries described here were almost exclusively of very high affinity, with K d values in the range of 10 Ϫ11 M. Three of the aptamers could be truncated significantly to a minimal length ranging from 23 to 29 nucleotides.…”

Section: ј-Fluoropyrimidine Rna-based Aptamers To Vegf 165mentioning

confidence: 99%

“…The incentive for performing SELEX experiments with 2Ј-F-pyrimidine RNA libraries, described in this report, was essentially 2-fold: first, we hoped to obtain nuclease-resistant aptamers that bind to VEGF with higher affinities than the 2Ј-NH 2 -pyrimidine-based aptamers. 2Ј-NH 2 modifications have been observed to decrease the stability of model DNA/DNA, RNA/ RNA, and RNA/DNA duplexes (35,36), while substitution of 2Ј-F in model duplexes dramatically increases their thermal stability (32,37,38). If 2Ј-NH 2 groups increase the conformational flexibility of oligonucleotides in general, the entropic cost of binding may limit the affinity of aptamers derived from 2Ј-NH 2 -pyrimidine RNA libraries (39).…”

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confidence: 99%

2′-Fluoropyrimidine RNA-based Aptamers to the 165-Amino Acid Form of Vascular Endothelial Growth Factor (VEGF165)

Ruckman¹,

Green²,

Beeson³

et al. 1998

Journal of Biological Chemistry

664

295

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“…above [24][25][26]. Reaction products were resolved by polyacrylamide gel electrophoresis or HPLC, and 2Ј-amine acylation rates were obtained by fitting the fraction-acylated product to a pseudo-firstorder equation that accounts for parallel hydrolysis of the succinimidyl ester (15).…”

Section: Resultsmentioning

confidence: 99%

Catalysis of amide synthesis by RNA phosphodiester and hydroxyl groups

Chamberlin

Merino

Weeks

2002

Proc. Natl. Acad. Sci. U.S.A.

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The functional groups found among the RNA bases and in the phosphoribose backbone represent a limited repertoire from which to construct a ribozyme active site. This work investigates the possibility that simple RNA phosphodiester and hydroxyl functional groups could catalyze amide bond synthesis. Reaction of amine groups with activated esters would be catalyzed by a group that stabilizes the partial positive charge on the amine nucleophile in the transition state. 2-Amine substitutions adjacent to 3-phosphodiester or 3-hydroxyl groups react efficiently with activated esters to form 2-amide and peptide products. In contrast, analogs in which the 3-phosphodiester is replaced by an uncharged phosphotriester or is constrained in a distal conformation react at least 100-fold more slowly. Similarly, a nucleoside in which the 3-hydroxyl group is constrained trans to the 2-amine is also unreactive. Catalysis of synthetic reactions by RNA phosphodiester and ribose hydroxyl groups is likely to be even greater in the context of a preorganized and solvent-excluding catalytic center. One such group is the 2-hydroxyl of the ribosome-bound P-site adenosine substrate, which is close to the amine nucleophile in the peptidyl synthesis reaction. Given ubiquitous 2-OH groups in RNA, there exists a decisive advantage for RNA over DNA in catalyzing reactions of biological significance. N atural RNA molecules catalyze reactions at phosphodiester centers (1) and, in the case of the ribosome large subunit, form the catalytic active site for amide bond synthesis (2, 3). In vitro selection methods yield RNAs that catalyze diverse reactions, including amide bond formation (4-6). Catalysis at any RNA active site must reflect chemical limitations imposed by having four relatively similar building blocks and lacking functional groups with pKas in the physiological range.Within this set of chemical constraints, catalytic RNAs employ strategies including juxtaposition and orientation of substrates (7,8), incorporation of metal ion prosthetic groups (9, 10), perturbing the pKas of titratable base positions (11,12), and positioning 2Ј-hydroxyl groups to stabilize an oxyanion (13,14). The RNA phosphoribose backbone is also likely to play indirect roles in catalysis by functioning, for example, to position catalytic metal ions or to perturb the local environment at RNA bases. 2-Amine Acylation and Nucleotide FlexibilityA robust approach for monitoring local flexibility in RNA and DNA is based on substituting the unreactive 2Ј-hydroxyl with a more nucleophilic amine (15-17). The 2Ј-amine group serves as a chemical handle that can be selectively modified by using an activated ester. This amide-forming reaction is gated by the underlying nucleic acid structure such that 2Ј-amine substitutions at flexible nucleotides are more reactive than amine groups at constrained positions (Fig. 1A). For example, 2Ј-amine substitutions in the anticodon loop of tRNA Asp react efficiently to form the 2Ј-amide, whereas 2Ј-amine positions that form stable base pairs, ...

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Syntheses and Interactions of Oligodeoxyribonucleotides Containing 2′-Amino-2′-Deoxyuridine

Cited by 24 publications

References 18 publications

Nucleotides. Part LVII.. Synthesis of phosphoramidite building blocks of 2′‐amino‐2′‐deoxyribonucleosides: New compounds for oligonucleotide synthesis

Nucleotides. Part LVII.. Synthesis of phosphoramidite building blocks of 2′‐amino‐2′‐deoxyribonucleosides: New compounds for oligonucleotide synthesis

2′-Fluoropyrimidine RNA-based Aptamers to the 165-Amino Acid Form of Vascular Endothelial Growth Factor (VEGF165)

Catalysis of amide synthesis by RNA phosphodiester and hydroxyl groups

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