化学
寡核苷酸
碱基
鸟嘌呤
加合物
圆二色性
电喷雾电离
DNA
偶联反应
脱氧鸟苷
组合化学
磷酰胺
联轴节(管道)
芳基
钯
立体化学
质谱法
有机化学
核苷酸
生物化学
色谱法
催化作用
基因
作者
Alireza Omumi,Daniel G. Beach,Michael J. Baker,Wojciech Gabryelski,Richard A. Manderville
摘要
Direct radical addition reactions at the C(8)-site of 2'-deoxyguanosine (dG) can afford C(8)-Ar-dG adducts that are produced by carcinogenic arylhydrazines, polycyclic aromatic hydrocarbons, and certain phenolic toxins. Such modified nucleobases are also highly fluorescent for sensing applications and possess useful electron transfer properties. The site-specific synthesis of oligonucleotides containing the C(8)-Ar-G adduct can be problematic. These lesions are sensitive to acids and oxidants that are commonly used in solid-phase DNA synthesis and are too bulky to be accepted as substrates for enzymatic synthesis by DNA polymerases. Using the Suzuki-Miyaura cross-coupling reaction, we have synthesized a number of C(8)-Ar-G-modified oligonucleotides (dimers, trimers, decamers, and a 15-mer) using a range of arylboronic acids. Good to excellent yields were obtained, and the reaction is insensitive to the nature of the bases flanking the convertible 8-Br-G nucleobase, as both pyrimidines and purines are tolerated. The impact of the C(8)-Ar-G lesion was also characterized by electrospray ionization tandem mass spectrometry, UV melting temperature analysis, circular dichroism, and fluorescence spectroscopy. The C(8)-Ar-G-modified oligonucleotides are expected to be useful substrates for diagnostic applications and understanding the biological impact of the C(8)-Ar-G lesion.
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