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.

异种核酸是天然核酸的合成类似物，具有用于核酸药物以及作为正交遗传生物聚合物和益生元前体的潜力。虽然很少有无环核酸能与RNA和DNA稳定结合，但丝氨醇核酸(SNA)和L-苏氨醇核酸(L- a TNA)能稳定结合它们。在这里，我们公开了与 SNA 和与 L- a TNA 杂交的 RNA 的晶体结构。异源双链显示出展开的右手螺旋结构。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，因此螺旋间距很大。展开的螺旋结构源自核碱基与 L- a 的相邻主链之间的相互作用TNA 和 SNA 通过 CH-O 键。此外，SNA 和 L - a TNA 通过 C:G*G 平行 Hoogsteen 与 RNA 相互作用形成三链体结构。L- a TNA 和 SNA的 RNA 识别模式的独特结构特征应该在纳米技术、生物技术和生命起源前化学的基础研究中发挥作用。