Lown J W, Hanstock C C
Department of Chemistry, University of Alberta, Edmonton, Canada.
J Biomol Struct Dyn. 1985 Jun;2(6):1097-106. doi: 10.1080/07391102.1985.10507626.
Complete 1H-nmr assignment has been achieved of the stoichiometric 1:1 complex of the antitumor agent mitoxantrone with the duplex oligomer [d(CpGpCpG)]2. The techniques used included 2D-COSY, 1D-NOE and 2D-HH-INADEQUATE. Comparisons of 1H and 13C chemical shift changes upon addition of drug suggest symmetrical intercalative binding to the center of the tetramer. NOE difference measurements and 31P studies suggest binding of the terminal OH groups of the side chains to the central phosphate groups such that the methylene groups are proximate to C(3)6, C(3)6 and G(4)8 base protons all in the major groove. The data suggest that the side chains bind to the neighboring base pairs from the intercalation site. This is in accord with independent evidence of G,C base preference for binding from spectroscopic and electron microscopy studies.
已完成抗肿瘤药物米托蒽醌与双链寡聚体[d(CpGpCpG)]₂的化学计量比为1:1的复合物的¹H-核磁共振全归属。所采用的技术包括二维相关谱（2D-COSY）、一维核Overhauser效应（1D-NOE）和二维全同核相关谱（2D-HH-INADEQUATE）。添加药物后¹H和¹³C化学位移变化的比较表明，该药物以对称的嵌入方式结合到四聚体的中心。核Overhauser效应差异测量和³¹P研究表明，侧链的末端羟基与中心磷酸基团结合，使得亚甲基靠近均位于大沟中的C(3)6、C(3')6和G(4)8碱基质子。数据表明，侧链从嵌入位点与相邻碱基对结合。这与光谱学和电子显微镜研究中关于G、C碱基结合偏好的独立证据一致。
