Molecular recognition of poly(A) by small ligands: an alternative method of analysis reveals nanomolar, cooperative and shape-selective binding.
Molecular recognition of poly(A) by small ligands: an alternative method of analysis reveals nanomolar, cooperative and shape-selective binding.
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DOI：
10.1093/nar/gkn977
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发表时间：
2009-02
影响因子：
14.9
通讯作者：
Hud NV
中科院分区：
文献类型：
--
作者：
Cetinkol OP;Hud NV
最近发现一些药物样分子结合聚腺苷酸并诱导稳定的二级结构（Tm ≥ 60°C），即使这种RNA均聚物在不存在配体的情况下是单链的。在这里，我们报告了专门设计用于探索小分子与poly（A）的关联的实验结果。我们证明，第一个被发现与poly（dA）结合的小分子coralyne以出乎意料的高亲和力（Ka >107 M−1）结合，并且coralyne的新月形似乎是poly（A）结合所必需的。我们还表明，类似的配体的结合聚（A）可以是高度合作。对于一个特定的配体，需要至少六个配体分子来在室温下稳定聚（A）自身结构。这种高度协同的结合在非结构化和结构化聚（A）之间产生非常急剧的转变，作为配体浓度的函数。考虑到沃森-克里克和A·A双链体之间的连接是可耐受的，我们提出，聚（A）序列元件和适当的配体可以用于可逆地驱动DNA和RNA为基础的分子结构的转换，通过简单地稀释/浓缩样品约聚（A）-配体的“临界浓度”。由于活细胞中mRNA的3′-聚腺苷酸化，这里描述的配体也可能发现生物或医学应用。
A few drug-like molecules have recently been found to bind poly(A) and induce a stable secondary structure (Tm ≈ 60°C), even though this RNA homopolymer is single-stranded in the absence of a ligand. Here, we report results from experiments specifically designed to explore the association of small molecules with poly(A). We demonstrate that coralyne, the first small molecule discovered to bind poly(dA), binds with unexpectedly high affinity (Ka >107 M−1), and that the crescent shape of coralyne appears necessary for poly(A) binding. We also show that the binding of similar ligands to poly(A) can be highly cooperative. For one particular ligand, at least six ligand molecules are required to stabilize the poly(A) self-structure at room temperature. This highly cooperative binding produces very sharp transitions between unstructured and structured poly(A) as a function of ligand concentration. Given the fact that junctions between Watson–Crick and A·A duplexes are tolerated, we propose that poly(A) sequence elements and appropriate ligands could be used to reversibly drive transitions in DNA and RNA-based molecular structures by simply diluting/concentrating a sample about the poly(A)-ligand ‘critical concentration’. The ligands described here may also find biological or medicinal applications, owing to the 3′-polyadenylation of mRNA in living cells.
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影响因子：
3.6
作者：
Huang, KS;Haddadin, MJ;Kurth, MJ
通讯作者：
Kurth, MJ
影响因子：
3.9
作者：
Biver, Tarita;Ciatto, Carlo;Venturini, Marcella
通讯作者：
Venturini, Marcella
DOI：
10.1107/s0907444905015404
发表时间：
2005-07-01
影响因子：
2.2
作者：
Canals, A;Purciolas, M;Coll, M
通讯作者：
Coll, M
影响因子：
2.9
作者：
LEE, JS;LATIMER, LJP;HAMPEL, KJ
通讯作者：
HAMPEL, KJ
影响因子：
4.5
作者：
Dower, K;Kuperwasser, N;Rosbash, M
通讯作者：
Rosbash, M