Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149, Münster, Germany.
Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie neuer Materialien, Universität Osnabrück, Barbarastrasse 7, 49069, Osnabrück, Germany.
Chemistry. 2022 Feb 16;28(9):e202103872. doi: 10.1002/chem.202103872. Epub 2022 Jan 14.
Anomeric base pairs in heterochiral DNA with strands in the α-d and β-d configurations and homochiral DNA with both strands in α-d configuration were functionalized. The α-d anomers of 2'-deoxyuridine and 7-deaza-2'-deoxyadenosine were synthesized and functionalized with clickable octadiynyl side chains. Nucleosides were protected and converted to phosphoramidites. Solid-phase synthesis furnished 12-mer oligonucleotides, which were hybridized. Pyrene click adducts display fluorescence, a few of them with excimer emission. T values and thermodynamic data revealed the following order of duplex stability α/α-d≫β/β-d≥α/β-d. CD spectra disclosed that conformational changes occur during hybridization. Functionalized DNAs were modeled and energy minimized. Clickable side chains and bulky click adducts are well accommodated in the grooves of anomeric DNA. The investigation shows for the first time that anomeric DNAs can be functionalized in the same way as canonical DNA for potential applications in nucleic acid chemistry, chemical biology, and DNA material science.
具有α-d 和 β-d 构型链的异手性 DNA 和两条链均为 α-d 构型的同手性 DNA 的糖苷键对被功能化。2'-脱氧尿苷和 7-脱氮-2'-脱氧腺苷的α-d 差向异构体被合成并与可点击的辛二炔侧链功能化。核苷被保护并转化为磷酰胺。固相合成提供了 12 个核苷酸的寡核苷酸，然后进行杂交。芘点击加合物显示荧光，其中一些具有激基发射。T 值和热力学数据揭示了双链体稳定性的以下顺序：α/α-d≫β/β-d≥α/β-d。圆二色谱揭示了在杂交过程中发生构象变化。功能化的 DNA 被建模并进行能量最小化。可点击的侧链和庞大的点击加合物可以很好地容纳在糖苷键对 DNA 的沟槽中。该研究首次表明，糖苷键对 DNA 可以像经典 DNA 一样进行功能化，有望应用于核酸化学、化学生物学和 DNA 材料科学。
