Shafer R H, Roques B P, LePecq J B, Delepierre M
Unité de Physicochimie Macromoleculaire, Institut Gustave Roussy, Villejuif.
Eur J Biochem. 1988 Apr 15;173(2):377-82. doi: 10.1111/j.1432-1033.1988.tb14009.x.
The interaction of chromomycin A3 (an antitumor antibiotic) with right-handed and left-handed polynucleotides has been studied by absorbance, fluorescence, circular dichroism, 31P-NMR and 1H-NMR techniques. Binding to either the B form of poly(dG-dC) or the Z form of poly(dG-m5dC) shifts the absorbance maximum to higher wavelength and enhances the fluorescence of the drug. Circular dichroic spectra of solutions containing various concentrations of chromomycin A3 and fixed concentrations of either B or Z polynucleotides show well defined isoelliptic points at similar wavelengths. At the isoelliptic point, the drug complex with B DNA exhibits positive ellipticity while with Z DNA it exhibits negative ellipticity. 31P-NMR spectra of the chromomycin A3 complex with the Z form of poly(dG-m5dC) demonstrate that the Z conformation is retained in the drug complex up to one molecule drug/four base pairs. At Mg2+ concentrations lower than that necessary to stabilize the left-handed conformation of poly(dG-m5dC) alone, 31P analysis shows that chromomycin A3 can bind simultaneously to both the B and Z conformations of poly(dG-m5dC), with no effect on the B-Z equilibrium. These data demonstrate that chromomycin A3 binds to left-handed poly(dG-m5dC) with retention of the left-handed conformation up to saturating drug concentrations.
采用吸光度、荧光、圆二色性、31P - NMR和1H - NMR技术研究了嗜铬霉素A3（一种抗肿瘤抗生素）与右手螺旋和左手螺旋多核苷酸的相互作用。与聚（dG - dC）的B型或聚（dG - m5dC）的Z型结合会使最大吸光度移向更高波长，并增强药物的荧光。含有不同浓度嗜铬霉素A3和固定浓度的B型或Z型多核苷酸的溶液的圆二色光谱在相似波长处显示出明确的等椭圆点。在等椭圆点处，与B - DNA形成的药物复合物呈现正椭圆率，而与Z - DNA形成的药物复合物呈现负椭圆率。嗜铬霉素A3与聚（dG - m5dC）的Z型形成的复合物的31P - NMR光谱表明，在高达一个分子药物/四个碱基对的情况下，Z构象在药物复合物中得以保留。在Mg2 +浓度低于单独稳定聚（dG - m5dC）左手构象所需浓度时，31P分析表明嗜铬霉素A3可以同时与聚（dG - m5dC）的B型和Z型构象结合，而对B - Z平衡没有影响。这些数据表明，嗜铬霉素A3与左手螺旋聚（dG - m5dC）结合时，直至药物浓度达到饱和，左手螺旋构象仍得以保留。
