Deshmukh H M, Joglekar S P, Broom A D
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City 84112, USA.
Bioconjug Chem. 1995 Sep-Oct;6(5):578-86. doi: 10.1021/bc00035a012.
Incorporation of an intercalating agent into an oligodeoxynucleotide (ODN) has the potential to enhance binding affinity upon duplex formation, to increase ODN hydrophobicity, and to enhance resistance to nuclease hydrolysis. Site-specific intercalation has been achieved through the synthesis of 2'-O-(anthraquinone-2-methyl)adenosine(rA*) and its incorporation into the palindromic dodecanucleotide d(CGCrA*CATGTGCG). Melting temperature, CD spectra, 1D and 2D (DQF-COSY and NOESY) NMR spectra, and molecular models were obtained and compared with the unmodified dodecamer. The data clearly establish that intercalation of the anthraquinone ring into a predominantly B-type helix occurs between the A4-T9 and C5-G8 base pairs, significantly stabilizing the duplex and enhancing the hydrophobicity of the ODN.
将嵌入剂掺入寡脱氧核苷酸（ODN）中，有可能在双链体形成时增强结合亲和力、增加ODN的疏水性，并增强对核酸酶水解的抗性。通过合成2'-O-（蒽醌-2-甲基）腺苷（rA*）并将其掺入回文十二聚体d（CGCrA*CATGTGCG）中，实现了位点特异性嵌入。获得了熔解温度、圆二色光谱、一维和二维（DQF-COSY和NOESY）核磁共振光谱以及分子模型，并与未修饰的十二聚体进行了比较。数据清楚地表明，蒽醌环嵌入主要为B型的螺旋结构中，发生在A4-T9和C5-G8碱基对之间，显著稳定了双链体并增强了ODN的疏水性。
