Guanines are a quartet's best friend: impact of base substitutions on the kinetics and stability of tetramolecular quadruplexes.
Guanines are a quartet's best friend: impact of base substitutions on the kinetics and stability of tetramolecular quadruplexes.
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DOI：
10.1093/nar/gkm111
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发表时间：
2007
影响因子：
14.9
通讯作者：
Mergny JL
中科院分区：
文献类型：
--
作者：
Gros J;Rosu F;Amrane S;De Cian A;Gabelica V;Lacroix L;Mergny JL
可以用带有三个或更多鸟嘌呤链段的短寡核苷酸形成平行的四分子四链体。我们分析了平行四链的序列变体的性质，其中中心块的每个鸟嘌呤被系统地用不同的碱基取代。在100多个不同的序列中评估了12种类型的替换。我们对所有四聚体进行了比较动力学分析。使用电喷雾质谱仪来计算内部阳离子的数量，这是有效四分体数量的指示器。一般来说，单一取代的存在对四链稳定性有很强的有害影响，导致四链寿命/热稳定性降低，缔合速率常数降低。我们证明了这些四链的缔合速率常数随修饰位置和类型的不同而有极大的差异。这些结果表明，大多数鸟嘌呤取代基对四分子四链结构是有害的。尽管在一些核磁共振和X射线结构中存在定义明确的非鸟嘌呤碱四元组，但我们的数据表明，大多数非鸟嘌呤四元组不利于结构稳定，并且这些四元组是依靠邻近的G-四元组提供的对接平台形成的。两个值得注意的例外是8-溴-鸟嘌呤(X)和6-甲基-异黄蝶呤(P)取代，当5‘端存在时，这两个取代可以加速10倍的四链形成。这里汇编的热力学和动力学数据对于设计具有可调缔合/解离性质的DNA四链组件具有很高的价值。
Parallel tetramolecular quadruplexes may be formed with short oligodeoxynucleotides bearing a block of three or more guanines. We analyze the properties of sequence variants of parallel quadruplexes in which each guanine of the central block was systematically substituted with a different base. Twelve types of substitutions were assessed in more than 100 different sequences. We conducted a comparative kinetic analysis of all tetramers. Electrospray mass spectrometry was used to count the number of inner cations, which is an indicator of the number of effective tetrads. In general, the presence of a single substitution has a strong deleterious impact on quadruplex stability, resulting in reduced quadruplex lifetime/thermal stability and in decreased association rate constants. We demonstrate extremely large differences in the association rate constants of these quadruplexes depending on modification position and type. These results demonstrate that most guanine substitutions are deleterious to tetramolecular quadruplex structure. Despite the presence of well-defined non-guanine base quartets in a number of NMR and X-ray structures, our data suggest that most non-guanine quartets do not participate favorably in structural stability, and that these quartets are formed only by virtue of the docking platform provided by neighboring G-quartets. Two notable exceptions were found with 8-bromo-guanine (X) and 6-methyl-isoxanthopterin (P) substitutions, which accelerate quadruplex formation by a factor of 10 when present at the 5′ end. The thermodynamic and kinetic data compiled here are highly valuable for the design of DNA quadruplex assemblies with tunable association/dissociation properties.
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影响因子：
14.9
作者：
Mergny JL;Li J;Lacroix L;Amrane S;Chaires JB
通讯作者：
Chaires JB
影响因子：
2.9
作者：
Hawkins, ME;Pfleiderer, W;Knutson, JR
通讯作者：
Knutson, JR
影响因子：
5.7
作者：
Pan, BC;Xiong, Y;Sundaralingam, M
通讯作者：
Sundaralingam, M
影响因子：
3.4
作者：
Driscoll, SL;Hawkins, ME;Laws, WR
通讯作者：
Laws, WR
影响因子：
10.5
作者：
Duquette, ML;Handa, P;Maizels, N
通讯作者：
Maizels, N