Luck G, Reinert K E, Baguley B, Zimmer C
Akademie der Wissenschaften der DDR, Zentralinstitut für Mikrobiologie und Experimentelle Therapie, Jena, G.D.R.
J Biomol Struct Dyn. 1987 Jun;4(6):1079-94. doi: 10.1080/07391102.1987.10507699.
Binding to DNA's of the non-intercalative ligands SN-6999 and SN-18071 has been studied by means of circular dichroism, UV absorption, thermal melting and for SN-6999 by viscosity measurements. Both antitumour drugs show a preference for dA.dT rich DNA's, but the base pair selectivity of SN-18071 is lower as indicated by some affinity to dG.dC containing duplex DNA. The dA.dT base pair specificity of SN-6999 is comparable to that of netropsin. It forms very stable complexes with dA.dT containing duplex DNA and competes with netropsin binding on DNA. The ligands SN-18071 and pentamidine are totally released from their complexes with poly(dA-dT).poly(dA-dT) by competitive netropsin binding. The results demonstrate that hydrogen bonding capacity of the ligand in addition to other factors strongly contribute to the base sequence specificity in the recognition process of the ligand with DNA. A binding model of SN-6999 with five dA.dT pairs in the minor groove of B-DNA is suggested.
已通过圆二色性、紫外吸收、热变性研究了非嵌入配体SN - 6999和SN - 18071与DNA的结合情况，对于SN - 6999还进行了粘度测量。这两种抗肿瘤药物都表现出对富含dA.dT的DNA的偏好，但SN - 18071的碱基对选择性较低，这体现在它对含dG.dC的双链DNA有一定亲和力。SN - 6999的dA.dT碱基对特异性与纺锤菌素相当。它与含dA.dT的双链DNA形成非常稳定的复合物，并在DNA上与纺锤菌素竞争结合。通过竞争性的纺锤菌素结合，配体SN - 18071和喷他脒从它们与聚(dA - dT).聚(dA - dT)的复合物中完全释放出来。结果表明，除其他因素外，配体的氢键结合能力在配体与DNA的识别过程中对碱基序列特异性有很大贡献。提出了SN - 6999在B - DNA小沟中与五个dA.dT对的结合模型。
