Inducible alkylation of DNA by a quinone methide-peptide nucleic acid conjugate.
Inducible alkylation of DNA by a quinone methide-peptide nucleic acid conjugate.
复制标题
DOI：
10.1021/bi201492b
复制
发表时间：
2012-02-07
期刊：
影响因子：
2.9
通讯作者：
Rokita, Steven E.
中科院分区：
文献类型：
--
作者：
Liu, Yang;Rokita, Steven E.
甲基苯醌中间体(QM)的可逆烷基化反应避免了困扰大多数基于共价化学的试剂的不可逆消耗，并允许由热力学而不是目标结合动力学控制的特定部位反应。这一特性最初是用寡核苷酸QM结合物检测的，但广泛的应用取决于与细胞环境兼容的替代衍生物。现在，一种肽核酸(PNA)衍生物已经被构建，并被证明具有以受控方式递送反应性QM的同等能力。这种新的偶联物表现出对互补DNA序列的高选择性，即使当挑战包含单个T/T错配的替代序列时也是如此。只有当模板链存在时，非互补序列的烷基化才可能发生，以共同定位偶联物及其靶标。在本例中，为了有效的烷基化，目标的单链区域需要与QM共轭物相邻。最重要的是，PNA与其附着的QM之间形成的链内自加成物在与随后添加的选定目标反应之前，在水溶液中保持了超过8天的活性和可逆性。
The reversibility of alkylation by a quinone methide intermediate (QM) avoids the irreversible consumption that plagues most reagents based on covalent chemistry and allows for site specific reaction that is controlled by the thermodynamics rather than kinetics of target association. This characteristic was originally examined with an oligonucleotide QM conjugate but broad application depends on alternative derivatives that are compatible with a cellular environment. Now, a peptide nucleic acid (PNA) derivative has been constructed and shown to exhibit an equivalent ability to delivery the reactive QM in a controlled manner. This new conjugate demonstrates high selectivity for a complementary sequence of DNA even when challenged with an alternative sequence containing a single T/T mismatch. Alkylation of non-complementary sequences is only possible when a template strand is present to co-localize the conjugate and its target. For efficient alkylation in this example, a single-stranded region of the target is required adjacent to the QM conjugate. Most importantly, the intrastrand self adducts formed between the PNA and its attached QM remained active and reversible over more than eight days in aqueous solution prior to reaction with a chosen target added subsequently.
登录
查看更多内容
影响因子：
2.8
作者：
Peng, Xiaohua;Li, Hong;Seidman, Michael
通讯作者：
Seidman, Michael
影响因子：
2.7
作者：
Imoto, Shuhei;Hori, Tsuneaki;Nagatsugi, Fumi
通讯作者：
Nagatsugi, Fumi
影响因子：
15
作者：
Cai, JF;Li, XX;Taylor, JS
通讯作者：
Taylor, JS
影响因子：
1.8
作者：
KOCH, T;NAESBY, M;ORUM, H
通讯作者：
ORUM, H
影响因子：
4.7
作者：
Kumar, D;Veldhuyzen, WF;Rokita, SE
通讯作者：
Rokita, SE