Le Doan T, Guigues M, Toulmé J J, Hélène C
Biochim Biophys Acta. 1985 Aug 21;825(4):353-9. doi: 10.1016/0167-4781(85)90061-2.
The antitumoral derivative cisPt binds to DNA, as do its inactive analogs, trans- and dienPt. Structural damage introduced into DNA after reaction with the Pt derivatives were probed by using the peptide LysTrpLys. This peptide was used for its preferential binding to single-stranded structures (Brun, F., Toulmé, J.J. and Hélène, C. (1975) Biochemistry 14, 558-563). Phosphorescence lifetime measurements show that the Pt-induced heavy atom effects are quite similar in the three peptide-DNA-Pt complexes whatever the nature of the Pt derivative used. In contrast, fluorescence quenching strongly depends on the nature of the Pt derivatives. This quenching was therefore attributed to the stacking interactions engaged by the tryptophan residue with nucleic acid bases. A comparison of fluorescence quenching data for native and modified DNAs demonstrates that modification by dienPt has no effect on stacking interactions and that high levels of modifications by trans Pt are required to observe a change in stacking efficiency. In contrast modification by cis Pt induces the formation of strong stacking sites. The results strongly suggest the existence of locally opened regions in DNA modified by cis Pt.
抗肿瘤衍生物顺铂（cisPt）与其无活性类似物反式铂（transPt）和二烯铂（dienPt）一样，能与DNA结合。通过使用肽LysTrpLys来探测与铂衍生物反应后引入到DNA中的结构损伤。该肽因其优先结合单链结构而被使用（Brun, F., Toulmé, J.J. 和Hélène, C. (1975) Biochemistry 14, 558 - 563）。磷光寿命测量表明，无论使用何种铂衍生物，在三种肽 - DNA - 铂复合物中，铂诱导的重原子效应都非常相似。相比之下，荧光猝灭强烈依赖于铂衍生物的性质。因此，这种猝灭归因于色氨酸残基与核酸碱基之间的堆积相互作用。对天然DNA和修饰DNA的荧光猝灭数据进行比较表明，二烯铂修饰对堆积相互作用没有影响，而反式铂的高水平修饰才能观察到堆积效率的变化。相比之下，顺铂修饰会诱导形成强堆积位点。结果有力地表明，顺铂修饰的DNA中存在局部开放区域。
