Enhancing DNA Triple Helix Stability at Neutral pH by the Use of Oligonucleotides Containing a More Basic Deoxycytidine Analog

Abstract

COMMUNICATIONSover MgSO, and concentrated under reduced pressure. After separation by column chromatography (silica gel, hexane:EtOAc = 20:1), 12b (20mg. 0.11 mmol) and 13b (56 mg, 0.30 mmol) were isolated in 21 and 60% yield, respectively. as colorless oils.12b;'HNMR(30OMHz,CDCI3):6 =1.03(s,3H).2.19(dd,J=l5.0,7.

Targeting DNA with Triplexes

“…(2e) which has a pK of 6.86, closer to physiological pH [38][39][40][41]. Psoralen-linked oligonucleotides containing this base have been successfully targeted against a portion of the aromatase gene [38].…”

“…Several features seem important in this regard. Firstly, since it is known that C +q GC is more stable than T q AT [18][19][20][21], novel cytosine analogues with a hydrogen bond donor at a position equivalent to N3 should retain the positive charge either on the ring system, as in 2-aminopyridine [38][39][40][41], or added to a side group which may be attached to either N4 or C5 [59][60][61][62]. The importance of the positive charge suggests that the stability of T q AT might be improved by generating a charged analogue of T. However, since adjacent C +q GC triplets are known to be destabilising, due to repulsion between the charged groups, it may be necessary to prepare both charged and uncharged analogues of T and C, and determine the optimum arrangement of the charged derivatives.…”

“…Pyrimidine analogues for recognition of GC base pairs in a parallel triplex. a) the 5Me C + q GC triplet, b) pseudoisocytosine [27,28], c) 6-oxocytosine [31][32][33][34], d) pyrazine analogue [37], e) 2-aminopyridine [38][39][40][41]. In b) -e) the third strand base analogue is shown alone in the same orientation as in a), indicating the substituents that form hydrogen bonds to G. Purine analogues for recognition of GC base pairs in a parallel triplex.…”

Pyrrolidino DNA with Bases Corresponding to the 2‐Oxo Deletion Mutants of Thymine and Cytosine: Synthesis and Triplex‐Forming Properties

“…(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) (and at physiological pH completely protonated) analogue [10][11][12][13] or with a charge-neutral analogue of cytosine. [14][15][16][17][18] Several approaches address the targeting of pyrimidine-purine inversion sites with high affinity.…”

“…2-Aminopyridine had already previously been shown to be an excellent cytosine analogue in parallel triplexes in the deoxyribo backbone series. [10][11][12][13] In this article we report on the synthesis of the phosphoramidite building blocks of dp2P and dp2AP, their incorporation into TFOs as substitutes for T and C, respectively, and the evaluation of their triplex pairing properties. Finally we compare the results with those observed with the first generation of pyrrolidino pseudonucleosides.…”