Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230, Odense, Denmark.
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Org Biomol Chem. 2020 Sep 23;18(36):7213-7223. doi: 10.1039/d0ob01426e.
Xeno nucleic acids (XNAs) are artificial genetic systems based on sugar-modified nucleotides. Herein, we investigate double-headed nucleotides as a new XNA. A new monomer, AT, is presented, and together with previous double-headed nucleotide monomers, new nucleic acid motifs consisting of up to five consecutive A·T base pairs have been obtained. Sections composed entirely of double-headed nucleotides are well-tolerated within a DNA duplex and can condense the genetic information. For instance, a 13-mer duplex is condensed to an 11-mer modified duplex containing four double-headed nucleotides while simultaneously improving duplex thermal stability with +14.0 °C. Also, the transfer of information from double-headed to natural nucleotides by DNA polymerases has been examined. The first double-headed nucleoside triphosphate was prepared but could not be recognized and incorporated by the tested DNA polymerases. On the other hand, it proved possible for Therminator DNA polymerase to transfer the information of a double-headed nucleotide in a template sequence to natural DNA under controlled conditions.
异核酸（XNAs）是基于糖修饰核苷酸的人工遗传系统。在此，我们研究了双头核苷酸作为一种新型 XNA。提出了一种新的单体 AT，并且与以前的双头核苷酸单体一起，已经获得了由多达五个连续的 A·T 碱基对组成的新的核酸基序。完全由双头核苷酸组成的部分在 DNA 双链体中具有良好的耐受性，并且可以浓缩遗传信息。例如，13 -mer 双链体被浓缩为包含四个双头核苷酸的 11-mer 修饰双链体，同时提高双链体热稳定性，增加了+14.0°C。此外，还研究了 DNA 聚合酶将信息从双头核苷酸转移到天然核苷酸。虽然已经制备了第一个双头核苷三磷酸，但它不能被测试的 DNA 聚合酶识别和掺入。另一方面，在受控条件下，Therminator DNA 聚合酶证明可以将模板序列中双头核苷酸的信息转移到天然 DNA 上。
