Mitsui Tsuneo, Kimoto Michiko, Sato Akira, Yokoyama Shigeyuki, Hirao Ichiro
Research Center for Advanced Science and Technology, The University of Tokyo, Komaba, Meguro-ku, Tokyo 4-6-1 153-8904, Japan.
Bioorg Med Chem Lett. 2003 Dec 15;13(24):4515-8. doi: 10.1016/j.bmcl.2003.09.059.
To develop unnatural base pairs that function in replication, we designed 4-propynylpyrrole-2-carbaldehyde (designated as Pa') and synthesized the nucleoside derivatives of Pa'. The base pairing of Pa' with the partner, 9-methylimidazo[(4,5)-b]pyridine (Q), was compared to that of pyrrole-2-carbaldehyde (Pa), which was previously developed as a specific pairing partner of Q. The thermal stability of a DNA duplex containing the Q-Pa' pair and the incorporation efficiency of the Pa' substrate (dPa'TP) into DNA opposite Q by the Klenow fragment of Escherichia coli DNA polymerase I were improved, in comparison with those of the Q-Pa pair. These improvements result from the increased hydrophobicity and stacking stability of Pa' by the introduction of the propynyl group to Pa, providing valuable information for the further development of unnatural base pairs toward the expansion of the genetic alphabet.
为了开发能在复制过程中起作用的非天然碱基对，我们设计了4-丙炔基吡咯-2-甲醛（命名为Pa'）并合成了Pa'的核苷衍生物。将Pa'与配对碱基9-甲基咪唑并[(4,5)-b]吡啶（Q）的碱基配对情况，与之前开发的作为Q的特异性配对碱基的吡咯-2-甲醛（Pa）进行了比较。与Q-Pa碱基对相比，含有Q-Pa'碱基对的DNA双链体的热稳定性以及大肠杆菌DNA聚合酶I的Klenow片段将Pa'底物（dPa'TP）掺入与Q相对的DNA中的掺入效率均得到了提高。这些改进源于向Pa引入丙炔基后Pa'疏水性和堆积稳定性的增加，为进一步开发用于扩展遗传字母表的非天然碱基对提供了有价值的信息。
