Büning H, Altman J, Beck W, Zorbas H
Institut für Biochemie der Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, Germany.
Biochemistry. 1997 Sep 23;36(38):11408-18. doi: 10.1021/bi970741l.
The interaction of novel, tetrafunctional bisplatinum compounds with DNA was investigated. These compounds have bis(vicinal 1,2-diamines) as ligand. The reactions' efficiency, types of cross-links, alterations of the global DNA structure, and sequence selectivity differ significantly from the corresponding features of cisplatin. In particular, they form multiple complexes with dsDNA, which include intrastrand, interstrand and interhelical cross-links and cross-links over sticky ends. The novel compounds are able to untwist but not shorten dsDNA. The reactivity and adduct-forming efficiency of these compounds is, depending on the spacer length, 100-200-fold higher than that of cisplatin. As a consequence, interstrand cross-links are also formed to a higher extent. The chemical stability of the interstrand cross-links against cyanide ions, however, is weaker than that of interstrand cross-links formed by cisplatin, suggesting that each platinum sphere of a bisplatinum compound forms intrastrand cross-links. With dsDNA, they show a preference toward purines, particularly guanines, but they apparently are also coordinated to other nucleobases. Their sequence selectivity toward dsDNA is higher than that of cisplatin. Thus, the novel compounds extend the spectrum of alternative platinum-based compounds with chemical features different from cisplatin.
研究了新型四官能双铂化合物与DNA的相互作用。这些化合物以双（邻位1,2 - 二胺）作为配体。反应效率、交联类型、整体DNA结构的改变以及序列选择性与顺铂的相应特征有显著差异。特别是，它们与双链DNA形成多种复合物，包括链内、链间和螺旋间交联以及粘性末端交联。这些新型化合物能够解开双链DNA的螺旋但不会使其缩短。这些化合物的反应活性和加合物形成效率，取决于间隔长度，比顺铂高100 - 200倍。因此，链间交联也在更大程度上形成。然而，链间交联对氰离子的化学稳定性比顺铂形成的链间交联弱，这表明双铂化合物的每个铂球形成链内交联。对于双链DNA，它们表现出对嘌呤，特别是鸟嘌呤的偏好，但显然也与其他碱基配位。它们对双链DNA的序列选择性高于顺铂。因此，这些新型化合物扩展了具有不同于顺铂化学特征的替代铂基化合物的范围。
