The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2

The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2
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DOI:
10.1093/nar/26.9.2237
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发表时间:
1998-05-01
影响因子:
14.9
通讯作者:
Marquez, VE
Marquez, VE
中科院分区:
生物学2区
文献类型:
--
作者:
Ikeda, H;Fernandez, R;Marquez, VE

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采用紫外热熔融研究、圆二色谱和核磁共振谱来评估对映糖构象对Dickerson-Drew十二聚体双链体{[d(CGCGAATTCGCG)](2),(ODN 1)}的典型B-DNA构象稳定性的贡献。通过使用3 '-内(北)2'-氟-2 '-脱氧呋喃核糖基胸腺嘧啶(1)或2'-内(南)2 '-氟-2'-脱氧阿拉伯呋喃糖基胸腺嘧啶(2),合成了具有有利于不同糖构象的修饰的胸苷单元的ODN 1的不同寡脱氧核苷酸版本。结果表明,两个南胸苷极大地稳定了双螺旋,而两个北胸苷通过在双螺旋中间诱导更像A的构象而使其不稳定。在同一寡核苷酸中使用南北胸苷构象异构体的组合甚至进一步使双螺旋不稳定,但不诱导构象变化。在B-DNA ODN中间建立可检测的A样构象的临界长度似乎是4 bp。我们的研究结果表明,操纵的构象的DNA在一个序列独立的方式是可能的。
UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex {[d(CGCGAATTCGCG)](2), (ODN 1)}. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'-endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'-endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible.