Kamiya Yukiko, Satoh Tadashi, Kodama Atsuji, Suzuki Tatsuya, Murayama Keiji, Kashida Hiromu, Uchiyama Susumu, Kato Koichi, Asanuma Hiroyuki
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Commun Chem. 2020 Nov 6;3(1):156. doi: 10.1038/s42004-020-00400-2.
Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH-O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.
异源核酸是天然核酸的合成类似物，有潜力用于核酸药物、作为正交遗传生物聚合物和益生元前体。尽管很少有非环状核酸能与RNA和DNA稳定结合，但丝氨醇核酸（SNA）和L-苏氨醇核酸（L-αTNA）能与它们稳定结合。在此，我们公布了RNA与SNA以及与L-αTNA杂交的晶体结构。异源双链体呈现出解旋的右手螺旋结构。与典型的A型双链体不同，异源双链体中的碱基对垂直于螺旋轴排列，因此螺旋螺距较大。解旋的螺旋结构源于L-αTNA和SNA的核碱基与相邻主链之间通过CH-O键的相互作用。此外，SNA和L-αTNA通过与RNA的C:G*G平行Hoogsteen相互作用形成三链结构。L-αTNA和SNA识别RNA模式的独特结构特征在纳米技术、生物技术和益生元化学基础研究中应会很有用。
