High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers.
High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers.
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DOI：
10.1093/nar/gkp437
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发表时间：
2009-07
影响因子：
14.9
通讯作者：
Nielsen PE
中科院分区：
文献类型：
--
作者：
Hansen ME;Bentin T;Nielsen PE
虽然序列选择性的dsDNA靶向的三链体形成寡核苷酸已被广泛研究，只有很少的PNA-dsDNA三链体的性质所知，主要是由于竞争入侵过程。在这里，我们表明，当使用假异胞嘧啶取代，结合（寡）赖氨酸或9-氨基吖啶共轭适当修改，同型嘧啶PNA寡聚体结合互补dsDNA靶标通过三链体形成（亚）纳摩尔亲和力（在pH 7.2，150 mM Na+）。结合亲和力可以通过改变pH、PNA寡聚体长度、PNA净电荷和/或通过用假异胞嘧啶取代胞嘧啶以及DNA嵌入剂9-氨基吖啶的缀合来调节超过1000倍。此外，9-氨基吖啶缀合也强烈增强三链体侵入。完全匹配的靶标与含有单个中心定位错配的靶标的特异性超过150倍。这些数据一起支持在生理相关条件下使用高嘧啶PNA作为三链体靶向策略中的有效和序列选择性工具。
While sequence-selective dsDNA targeting by triplex forming oligonucleotides has been studied extensively, only very little is known about the properties of PNA–dsDNA triplexes—mainly due to the competing invasion process. Here we show that when appropriately modified using pseudoisocytosine substitution, in combination with (oligo)lysine or 9-aminoacridine conjugation, homopyrimidine PNA oligomers bind complementary dsDNA targets via triplex formation with (sub)nanomolar affinities (at pH 7.2, 150 mM Na+). Binding affinity can be modulated more than 1000-fold by changes in pH, PNA oligomer length, PNA net charge and/or by substitution of pseudoisocytosine for cytosine, and conjugation of the DNA intercalator 9-aminoacridine. Furthermore, 9-aminoacridine conjugation also strongly enhanced triplex invasion. Specificity for the fully matched target versus one containing single centrally located mismatches was more than 150-fold. Together the data support the use of homopyrimidine PNAs as efficient and sequence selective tools in triplex targeting strategies under physiological relevant conditions.
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DOI：
10.1073/pnas.92.13.5798
发表时间：
1995-06-20
影响因子：
11.1
作者：
GRYAZNOV, SM;LLOYD, DH;WILSON, WD
通讯作者：
WILSON, WD
影响因子：
14.9
作者：
Brunet, E;Corgnali, M;Giovannangeli, C
通讯作者：
Giovannangeli, C
影响因子：
14.9
作者：
Bentin T;Hansen GI;Nielsen PE
通讯作者：
Nielsen PE
DOI：
10.1073/pnas.90.5.1667
发表时间：
1993-03-01
影响因子：
11.1
作者：
CHERNY, DY;BELOTSERKOVSKII, BP;NIELSEN, PE
通讯作者：
NIELSEN, PE
DOI：
10.1073/pnas.92.7.2637
发表时间：
1995-03-28
影响因子：
11.1
作者：
DEMIDOV, VV;YAVNILOVICH, MV;NIELSEN, PE
通讯作者：
NIELSEN, PE