Methyl group configuration on acyclic threoninol nucleic acids (aTNAs) impacts supramolecular properties
Methyl group configuration on acyclic threoninol nucleic acids (aTNAs) impacts supramolecular properties
复制标题
无环苏氨醇核酸 (aTNAs) 上的甲基构型影响超分子特性
DOI：
10.1039/d2ob00266c
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Asanuma Hiroyuki
中科院分区：
文献类型：
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作者：
Murayama Keiji;Kashida Hiromu;Asanuma Hiroyuki
我们已经合成了无环苏氨酸醇核酸（alloo -aTNAs）和人工异种核酸（XNAs），它们是无环苏氨酸醇核酸（aTNAs）的非对映体，并研究了它们的超分子性质。异体aTNAs以反平行的方式形成同源双链，但热稳定性低于DNA，而aTNAs形成非常稳定的同源双链。同种异体aTNAs与互补的aTNAs和丝氨酸醇核酸（SNA）形成双链。L-allo-aTNA对L-aTNA的亲和力最高，对D-aTNA的亲和力最低，SNA为中间亲和力。d - alloo - atna的亲和力则相反。圆二色性测量显示，L-和D-allo-aTNAs分别具有弱的右旋和左旋螺旋。allo-aTNAs的弱螺旋度可能解释了这些XNAs的弱手性区分，这与具有强螺旋正交性的aTNAs形成对比。L-allo-aTNA/RNA和L-allo-aTNA/L-allo-aTNA的能量最小化结构表明，allo-aTNA链上的甲基不利于双链的形成。相反，L-aTNA上的甲基可能通过疏水效应和范德华相互作用来稳定双相结构。由此可见，甲基在XNA支架上的构型对其杂交能力和结构有着意想不到的巨大影响。
We have synthesized acyclic allo-threoninol nucleic acids (allo-aTNAs), artificial xeno-nucleic acids (XNAs) that are diastereomers of acyclic threoninol nucleic acids (aTNAs), and have investigated their supramolecular properties. The allo-aTNAs formed homo-duplexes in an antiparallel manner but with lower thermal stability than DNA, whereas aTNAs formed extremely stable homo-duplexes. The allo-aTNAs formed duplexes with complementary aTNAs and serinol nucleic acid (SNA). The affinities of L-allo-aTNA were the highest for L-aTNA and the lowest for D-aTNA, with SNA being intermediate. The affinities of D-allo-aTNA were the reverse. Circular dichroism measurements revealed that L- and D-allo-aTNAs had weak right-handed and left-handed helicities, respectively. The weak helicity of allo-aTNAs likely explains the poor chiral discrimination of these XNAs, which is in contrast to aTNAs that have strong helical orthogonality. Energy-minimized structures of L-allo-aTNA/RNA and L-allo-aTNA/L-allo-aTNA indicated that the methyl group on the allo-aTNA strand is unfavourable for duplex formation. In contrast, the methyl group on L-aTNA likely stabilizes the duplex structure via hydrophobic effects and van der Waals interactions. Thus, the configuration of the methyl group on the XNA scaffold had an unexpectedly large impact on the hybridization ability and structure.