Fritzsche H, Triebel H, Chaires J B, Dattagupta N, Crothers D M
Biochemistry. 1982 Aug 17;21(17):3940-6. doi: 10.1021/bi00260a006.
The structure of iremycin [10-(alpha-L-rhodosaminyl)-gamma-rhodomycinone] hydrochloride has been confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. We studied the interaction of iremycin and the related compound daunomycin with DNA by transient electric dichroism and by sedimentation analysis of supercoiled closed duplex DNA. The apparent length increase of sonicated calf thymus DNA (150 +/- 20 base pairs) in 2.5 mM sodium cacodylate buffer (pH 7) at 12 degrees C was determined to be 0.40 +/- 0.02 nm/bound drug). The Cu(II) complex of iremycin with a metal/drug ratio of 0.7 induces a length increase of DNA of 0.44 +/- 0.02 nm/added drug. The alignment of the iremycin chromophore with respect to the DNA helix axis was determined from the electric dichroism of the complex. The tilt (long axis) and twist (short axis) of the chromophore are both 28 +/- 4 degrees, whereas for daunomycin the long axis is perpendicular to the helix axis and the short axis is twisted by about 25 degrees. Intercalation of iremycin between DNA base pairs is supported by unwinding of the supercoiled closed duplex form of pBR 322 plasmid DNA from Escherichia coli. In 2.5 mM sodium cacodylate buffer at pH 7 and at 25 degrees C, the unwinding induced by iremycin is 15.0 +/- 1.5 degrees/bound drug. Under identical conditions daunomycin shows on unwinding angle of 15.4 +/- 1.5 degrees. The superhelical density of pBR 322 DNA (sigma 0) was determined to be -0.087 +/- 0.002 at standard conditions (0.2 M NaCl, 37 degrees C).
盐酸艾瑞霉素[10-(α-L-鼠李糖胺基)-γ-红霉酮]的结构已通过1H和13C核磁共振（NMR）光谱得到证实。我们通过瞬态电二色性以及超螺旋闭环双链DNA的沉降分析，研究了艾瑞霉素及相关化合物柔红霉素与DNA的相互作用。在12℃下，2.5 mM二甲胂酸钠缓冲液（pH 7）中超声处理的小牛胸腺DNA（150±20个碱基对）的表观长度增加量经测定为0.40±0.02 nm/结合药物）。金属/药物比率为0.7的艾瑞霉素铜（II）配合物使DNA长度增加0.44±0.02 nm/添加药物。根据配合物的电二色性确定了艾瑞霉素发色团相对于DNA螺旋轴的排列。发色团的倾斜（长轴）和扭转（短轴）均为28±4度，而对于柔红霉素，长轴垂直于螺旋轴，短轴扭转约25度。来自大肠杆菌的pBR 322质粒DNA的超螺旋闭环形式的解旋支持了艾瑞霉素插入DNA碱基对之间。在pH 7的2.5 mM二甲胂酸钠缓冲液中，25℃下，艾瑞霉素诱导的解旋为15.0±1.5度/结合药物。在相同条件下，柔红霉素的解旋角为15.4±1.5度。在标准条件（0.2 M NaCl，37℃）下，pBR 322 DNA的超螺旋密度（σ0）经测定为-0.087±0.002。
