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Synthesis and Pairing Properties of 3′‐Deoxyribopyranose (4′→2′)‐Oligonucleotides (‘ p ‐DNA')
Author(s) -
Ackermann Damian,
Pitsch Stefan
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200205)85:5<1443::aid-hlca1443>3.0.co;2-u
Subject(s) - chemistry , oligonucleotide , thymine , dna , nucleobase , cytosine , stereochemistry , guanine , rna , base pair , nucleotide , biochemistry , gene
The preparation and the pairing properties of the new 3′‐deoxyribopyranose (4′→2′)‐oligonucleotide (= p ‐DNA) pairing system, based on 3′‐deoxy‐ β ‐ D ‐ribopyranose nucleosides is presented. D ‐Xylose was efficiently converted to the prefunctionalized 3‐deoxyribopyranose derivative 4‐ O ‐[( tert ‐butyl)dimethylsilyl]‐3‐deoxy‐ D ‐ribopyranose 1,2‐diacetate 8 (obtained as a 4 : 1 mixture of α ‐ and β ‐ D ‐anomers; Scheme 1 ). From this sugar building block, the corresponding, appropriately protected thymine, guanine, 5‐methylcytosine, and purine‐2,6‐diamine nucleoside phosphoramidites 29 – 32 were prepared in a minimal number of steps ( Schemes 2–4 ). These building blocks were assembled on a DNA synthesizer, and the corresponding p ‐DNA oligonucleotides were obtained in good yields after a one‐step deprotection under standard conditions, followed by HPLC purification ( Scheme 5 and Table 1 ). Qualitatively, p ‐DNA shows the same pairing behavior as p ‐RNA, forming antiparallel, exclusively Watson‐Crick ‐paired duplexes that are much stronger than corresponding DNA duplexes. Duplex stabilities within the three related ( i.e. , based on ribopyranose nucleosides) oligonucleotide systems p ‐RNA, p ‐DNA, and 3′‐ O ‐Me‐ p ‐RNA were compared with each other ( Table 2 ). Intrinsically, p ‐RNA forms the strongest duplexes, followed by p ‐DNA, and 3′‐ O ‐Me‐ p ‐RNA. However, by introducing the nucleobases purine‐2,6‐diamine (D) and 5‐methylcytosine (M) instead of adenine and cytosine, a substantial increase in stability of corresponding p ‐DNA duplexes was observed.