Formation of a PNA2-DNA2 hybrid quadruplex
Formation of a PNA2-DNA2 hybrid quadruplex
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DOI：
10.1021/ja028323d
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发表时间：
2003-04-09
影响因子：
15
通讯作者：
Armitage, BA
中科院分区：
文献类型：
--
作者：
Datta, B;Schmitt, C;Armitage, BA
DNA 鸟嘌呤 (G) 四链体通过核酸双链体和三链体中遇到的氢键方案的有趣变化而稳定。在尝试使用这种分子识别模式时，我们靶向由Oxytricha nova端粒序列d(G(4)T(4)G(4))与具有同源而非互补序列的肽核酸(PNA)探针形成的二聚体G-四链体。 UV-vis 和 CD 光谱表明 PNA 和 DNA 之间形成了具有 G 四联体的稳定杂合体。杂交体的四链特征和链的相对方向通过荧光共振能量转移（FRET）实验确定。 FRET 结果表明 (i) 两条 PNA 链彼此平行，(ii) 两条 DNA 链彼此平行，以及 (iii) DNA 链的 5' 末端与 PNA 链的 N 末端对齐。所得的 PNA(2)-DNA(2) 四链体显示出 Na+ 优于 Li+，并且显示出与杂交体中交替的 PNA 和 DNA 链一致的热力学行为。这种新型超分子结构的形成展示了一种新的高亲和力DNA识别机制，扩大了PNA分子识别的范围。
DNA guanine (G) quadruplexes are stabilized by an interesting variation of the hydrogen-bonding schemes encountered in nucleic acid duplexes and triplexes. In an attempt to use this mode of molecular recognition, we target a dimeric G-quadruplex formed by the Oxytricha nova telomeric sequence d(G(4)T(4)G(4)) with a peptide nucleic acid (PNA) probe having a homologous rather than complementary sequence. UV-vis and CD spectroscopy reveal that a stable hybrid possessing G-quartets is formed between the PNA and DNA. The four-stranded character of the hybrid and the relative orientation of the strands is determined by fluorescence resonance energy transfer (FRET) experiments. FRET results indicate that (i) the two PNA strands are parallel to each other, (ii) the two DNA strands are parallel to each other, and (iii) the 5'-termini of the DNA strands align with the N-termini of the PNA strands. The resulting PNA(2)-DNA(2) quadruplex shows a preference of Na+ over Li+ and displays thermodynamic behavior consistent with alternating PNA and DNA strands in the hybrid. The formation of this novel supramolecular structure demonstrates a new high-affinity DNA recognition mechanism and expands the scope of molecular recognition by PNA.