Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3890, USA.
Inorg Chem. 2011 Dec 5;50(23):11929-37. doi: 10.1021/ic200855p. Epub 2011 Nov 7.
Peptide nucleic acid (PNA) is a synthetic analogue of DNA, which has the same nucleobases as DNA but typically has a backbone based on aminoethyl glycine (Aeg). PNA forms duplexes by Watson Crick hybridization. The Aeg-based PNA duplexes adopt a chiral helical structure but do not have a preferred handedness because they do not contain a chiral center. An L-lysine situated at the C-end of one or both strands of a PNA duplex causes the duplex to preferably adopt a left-handed structure. We have introduced into the PNA duplexes both a C-terminal L-lysine and one or two PNA monomers that have a γ-(S)-methyl-aminoethyl glycine backbone, which is known to induce a preference for a right-handed structure. Indeed, we found that in these duplexes the γ-methyl monomer exerts the dominant chiral induction effect causing the duplexes to adopt a right-handed structure. The chiral PNA monomer had a 2,2':6',2''-terpyridine (Tpy) ligand instead of a nucleobase and PNA duplexes that contained one or two Tpys formed Cu(Tpy)(2) complexes in the presence of Cu(2+). The CD spectroscopy studies showed that these metal-coordinated duplexes were right-handed due to the chiral induction effect exerted by the S-Tpy PNA monomer(s) except for the cases when the Cu(Tpy)(2) complex was formed with Tpy ligands from two different PNA duplexes. In the latter case, the metal complex bridged the two PNA duplexes and the duplexes were left-handed. The results of this study show that the preferred handedness of a ligand-modified PNA can be switched as a consequence of metal coordination to the ligand. This finding could be used as a tool in the design of functional nucleic-acid based nanostructures.
肽核酸 (PNA) 是 DNA 的人工合成类似物，与 DNA 具有相同的碱基，但通常具有基于氨基乙基甘氨酸 (Aeg) 的骨架。PNA 通过 Watson-Crick 杂交形成双链体。基于 Aeg 的 PNA 双链体采用手性螺旋结构，但没有手性，因为它们不包含手性中心。位于 PNA 双链体的一个或两个末端的 L-赖氨酸使双链体优先采用左手结构。我们在 PNA 双链体中引入了 C 末端的 L-赖氨酸和一个或两个具有 γ-(S)-甲基氨基乙基甘氨酸骨架的 PNA 单体，已知该骨架诱导对右手结构的偏好。事实上，我们发现，在这些双链体中，γ-甲基单体发挥了主导的手性诱导作用，使双链体采用右手结构。手性 PNA 单体具有 2,2':6',2''-三联吡啶 (Tpy) 配体而不是碱基，并且含有一个或两个 Tpys 的 PNA 双链体在存在 Cu(2+)时形成 Cu(Tpy)(2) 配合物。圆二色性 (CD) 光谱研究表明，这些金属配位的双链体是右手性的，这是由于 S-Tpy PNA 单体(s) 施加的手性诱导作用，除非 Cu(Tpy)(2) 配合物是由两个不同的 PNA 双链体的 Tpy 配体形成的。在后一种情况下，金属配合物桥接了两个 PNA 双链体，双链体为左手性。这项研究的结果表明，由于与配体的金属配位，修饰配体的 PNA 的优选手性可以被切换。这一发现可用于设计基于功能核酸的纳米结构的工具。
