The Nonnatural Deoxyribonucleoside D3 Incorporated in an Intramolecular DNA Triplex Binds Sequence Specifically by Intercalation

The Nonnatural Deoxyribonucleoside D3 Incorporated in an Intramolecular DNA Triplex Binds Sequence Specifically by Intercalation
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掺入分子内 DNA 三链体的非天然脱氧核糖核苷 D3 通过插入特异性结合序列

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发表时间:
1993
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影响因子:
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通讯作者:
J. Feigon
J. Feigon
中科院分区:
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文献类型:
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作者:
K. Koshlap;Paul Gillespie;P. Dervan;J. Feigon

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Oligonucleotide-directed triple helix formation is one of the most powerful methods for the sequence-specific recognition of double-helical DNA. Pyrimidine oligonucleotides bind purine tracts in the major groove of DNA parallel to the purine Watson-Crick strand through the formation of specific Hoogsteen-type hydrogen bonds. Specificity is derived from thymine (T) recognition of adenine·thymine (A·T) base pairs (T·A·T triplet) and N3-protonated cytosine (C+) recognition of guanine-cytosine (G·C) base pairs (C + G·C triplets). The sequence-specific recognition of double-helical DNA by a third strand to form a triple helix is limited to mostly purine tracts. Although G in the third strand has been found to specifically bind to T·A, the lower stability of the G·T·A triplet and its dependence on the sequence of the neigh boring triplets reveals that this will have limitations. In an attempt to extend the recognition code to all four Watson-Crick base pairs, the nonnatural deoxyribonucleoside 1-(2-deoxy/ β-D-ribofuranosyl)-4-(3-benzamido)phenylimidazole [D_3] was synthesized and incorporated into pyrimidine DNA oligonucleotides (Figure 1a). It was found that D_3 selectively recognizes both T·A and C·G Watson-Crick base pairs within the pyrimidine·purine·pyrimidine triple-helix motif. This was also found to have a nearest neighbor dependence.