Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA Folding and Hammerhead Ribozyme Catalysis.
Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA Folding and Hammerhead Ribozyme Catalysis.
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DOI：
10.1021/jacs.7b05448
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发表时间：
2017-07-26
影响因子：
15
通讯作者：
Bong D
中科院分区：
文献类型：
--
作者：
Mao J;DeSantis C;Bong D
我们已经鉴定了具有两个(T2M)或四个(T4M)三聚氰胺环的三(2-氨基乙基)胺(Tren)衍生支架，这些支架可以靶向DNA/RNA中的寡聚T/U结构域。非结构化富含T的DNA与Tren衍生物协同折叠形成发夹状结构。T2M和T4M都是锤头状核酶家族中的功能开关，通过用富含U的序列进行茎或环替换而失活。这些锤头状核酶的断键催化作用可以通过茎二级结构的T2M/T4M折叠或环与茎之间的三级桥联作用来恢复。T2M/T4M结合位点的简单性使得能够对RNA中的变构进行编程，将寡聚-U结构域重新编码为潜在的二级结构或三级接触位点。与在伯胺上安装T2M基序的简便和通用方法相结合，本文描述的方法简化了合成变构核糖开关和小分子−核酸络合物的设计。
We have identified tris(2-aminoethyl)amine (tren)-derived scaffolds with two (t2M) or four (t4M) melamine rings that can target oligo T/U domains in DNA/RNA. Unstructured T-rich DNAs cooperatively fold with the tren derivatives to form hairpin-like structures. Both t2M and t4M act as functional switches in a family of hammerhead ribozymes deactivated by stem or loop replacement with a U-rich sequence. Catalysis of bond scission in these hammerhead ribozymes could be restored by putative t2M/t4M refolding of stem secondary structure or tertiary bridging interactions between loop and stem. The simplicity of the t2M/t4M binding site enables programming of allostery in RNAs, recoding oligo-U domains as potential sites for secondary structure or tertiary contact. In combination with a facile and general method for installation of the t2M motif on primary amines, the method described herein streamlines design of synthetic allosteric riboswitches and small molecule−nucleic acid complexes.
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