Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany.
J Am Chem Soc. 2010 Mar 24;132(11):4016-24. doi: 10.1021/ja910020n.
8-Aza-2'-deoxyisoguanosine (4) is the first fluorescent shape mimic of 2'-deoxyisoguanosine (1a); its fluorescence is stronger in alkaline medium than under neutral conditions. Nucleoside 4, which was synthesized from 8-aza-2'-deoxyguanosine via a 4,6-diamino intermediate after selective deamination, was incorporated in oligodeoxyribonucleotides using phosphoramidite 11. Duplexes with 4 x m(5)iC(d) (5-methyl-2'-deoxyisocytidine) base pairs are more stable than those incorporating dG-dC pairs, thereby expanding the genetic alphabet by a fluorescent orthogonal base pair. As demonstrated by T(m) measurements, the base pair stability decreases in the order m(5)iC(d) x 4 >> dG x 4 > dT x 4 > or = dC x 4 >> dA x 4. A better base pairing selectivity of 4 against the canonical nucleosides dT, dC, dA, and dG is observed than for the degenerated base pairing of 1a. The base pair stability changes can be monitored by nucleobase anion fluorescence sensing. The fluorescence change correlates to the DNA base pair stability. Oligonucleotide 5'-d(T(4)4(4)T(4)) (22), containing short runs of nucleoside 4, forms stable multistranded assemblies (ionophores) with K(+) in the central cavity. They are quite stable at elevated temperature but are destroyed at high pH value.
8-氮杂-2'-脱氧次黄嘌呤核苷（4）是第一个 2'-脱氧次黄嘌呤核苷（1a）的荧光构象模拟物；其在碱性介质中的荧光比中性条件下更强。核苷 4 是通过 8-氮杂-2'-脱氧鸟苷经选择性脱氨作用生成 4,6-二氨基中间产物后合成的，通过亚磷酰胺 11 掺入寡脱氧核苷酸中。与掺入 dG-dC 对的寡核苷酸相比，具有 4 x m(5)iC(d)（5-甲基-2'-脱氧异胞嘧啶）碱基对的双链体更稳定，从而通过荧光正交碱基对扩展遗传字母表。如 T(m)测量所示，碱基对稳定性的顺序为 m(5)iC(d) x 4 >> dG x 4 > dT x 4 > or = dC x 4 >> dA x 4。与 1a 的简并碱基配对相比，观察到 4 对典型核苷 dT、dC、dA 和 dG 的碱基配对选择性更好。碱基对稳定性的变化可以通过碱基阴离子荧光传感来监测。荧光变化与 DNA 碱基对稳定性相关。含有核苷 4 短链的寡核苷酸 5'-d(T(4)4(4)T(4))（22）在中央腔中与 K(+) 形成稳定的多链组装体（离子载体）。它们在高温下相当稳定，但在高 pH 值下会被破坏。
