Büning H, Altman J, Zorbas H, Beck W
Institut für Biochemie der Ludwig-Maximilians-Universität München, Munich, Germany.
J Inorg Biochem. 1999 Jul 15;75(4):269-79. doi: 10.1016/s0162-0134(99)00099-9.
Bis[platinum(II)] [Cl2Pt(LL)PtCl2] complexes 2,5 and 8 with chiral non-racemic ligands: 1a-c (LL = (R,R), (S,S) and (R,S) N,N'-bis(3,4-diaminobutyl)hexanediamide); 4a,b (LL = (R,R) and (S,S) N,N'-bis[3,4-bis(diaminobutyl)] urea); 7a-d (LL' = (R,R), (S,S), (R,S) and (S,R) 4,5-diamino-N-(3,4-diaminobutyl) pentanamide) and bis[platinum(IV)] complex 10-13 with ligands 1a,b and 4a,b have been prepared and characterized by IR, 1H, 13C and 195Pt NMR spectra. The interactions of 2a-c, 5a, 5b, 8a-d and 10a with dsDNA were investigated with the goal of examining whether the chirality, the nature of the spacer and the oxidation state have an influence on platinum-DNA binding properties. All the bis[platinum(II)] complexes form with dsDNA intra- and interstrand crosslinks and crosslinks over sticky ends, whereas the bis[platinum(IV)] complex 10a only forms intra- and interstrand crosslinks. The platinum-DNA coordination sites were determined by the T4 DNA polymerase footprinting method. The results show that all investigated bis(platinum) complexes have high preference towards distinct purines. All isomeric bis(amide) 2a-c and mono(amide) 8a-d complexes exhibit nearly the same binding pattern, whereas the ureide complexes 5a and 5b have other coordination sites with higher sequence preference. Interestingly, the ureides 5a and 5b differ in their coordination sites not only in comparison to the bis(amides) 2a-c and mono(amides) 8a-d, but also between each other. The bis[platinum(IV)] complex 10a also differs in coordination sites in comparison to all the bis[platinum(II)] compounds.
具有手性非外消旋配体的双[铂(II)] [Cl₂Pt(LL)PtCl₂]配合物2、5和8：1a - c（LL = (R,R)、(S,S)和(R,S) N,N'-双(3,4 - 二氨基丁基)己二酰胺）；4a、b（LL = (R,R)和(S,S) N,N'-双[3,4 - 双(二氨基丁基)]脲）；7a - d（LL' = (R,R)、(S,S)、(R,S)和(S,R) 4,5 - 二氨基 - N - (3,4 - 二氨基丁基)戊酰胺）以及具有配体1a、b和4a、b的双[铂(IV)]配合物10 - 13已被制备，并通过红外光谱、¹H、¹³C和¹⁹⁵Pt核磁共振光谱进行了表征。研究了2a - c、5a、5b、8a - d和10a与双链DNA的相互作用，目的是考察手性、间隔基的性质和氧化态是否对铂 - DNA结合特性有影响。所有双[铂(II)]配合物与双链DNA形成链内和链间交联以及粘性末端交联，而双[铂(IV)]配合物10a仅形成链内和链间交联。通过T4 DNA聚合酶足迹法确定了铂 - DNA配位位点。结果表明，所有研究的双(铂)配合物对不同嘌呤具有高度偏好性。所有异构双(酰胺) 2a - c和单(酰胺) 8a - d配合物表现出几乎相同的结合模式，而脲基配合物5a和5b具有其他配位位点，序列偏好性更高。有趣的是，脲基化合物5a和5b不仅与双(酰胺) 2a - c和单(酰胺) 8a - d在配位位点上不同，而且它们彼此之间也不同。双[铂(IV)]配合物10a与所有双[铂(II)]化合物相比，在配位位点上也有所不同。
