The preparation and the pairing properties of the new 3'-deoxyribopyranose (4' 3 2')-oligonucleotide ( p-DNA) pairing system, based on 3'-deoxy-b-d-ribopyranose nucleosides is presented. d-Xylose was efficiently converted to the prefunctionalized 3-deoxyribopyranose derivative 4-O-[(tert-butyl)dimethylsilyl]-3-deoxy-dribopyranose 1,2-diacetate 8 (obtained as a 4 : 1 mixture of aand b-d-anomers; Scheme 1). From this sugar building block, the corresponding, appropriately protected thymine, guanine, 5-methylcytosine, and purine-2,6diamine 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.