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抗肿瘤药物铂-喷他脒对质粒DNA限制性酶切位点识别的修饰作用

Modification of the recognition of restriction sites of plasmid DNA by the antitumor drug Pt-pentamidine.

作者信息

Pérez J M, González V M, Fuertes M A, Alonso C

机构信息

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Spain.

出版信息

Biochem Pharmacol. 1996 Sep 27;52(6):851-6. doi: 10.1016/0006-2952(96)00351-6.

DOI:10.1016/0006-2952(96)00351-6
PMID:8781502
Abstract

The rate of binding of the antineoplastic drugs Pt-pentamidine [(cis-PtCl2)3(pentamidine)3][PtCl4]2 and cis-DDP [cis-diamminedichloroplatimum(II)] to pUC8 DNA, as well as the effect of the binding of these platinum compounds on the cutting effectiveness of Bam HI, Hind III, and Sal I restriction endonucleases, were determined by flameless atomic absorption spectroscopy and gel electrophoresis, respectively. The results show that covalent DNA platination is 12% to 22% lower in DNA: Pt-pentamidine complexes than in DNA: cis-DDP at the same molar rate of platinum/nucleotide, and the number of Pt-pentamidine molecules bound to DNA is significantly lower in Pt-pentamidine: DNA complexes than in cis-DDP: DNA complexes. Although both compounds inhibit Bam HI cleavage of pUC8 DNA, Pt-pentamidine does not prevent the cutting activity of Hind III, in contrast with cis-DDP. Neither cis-DDP nor Pt-pentamidine inhibits the cutting activity of Sal I, whose recognition sequence neighbors the Bam HI and Hind III sites.

摘要

通过无火焰原子吸收光谱法和凝胶电泳法分别测定了抗肿瘤药物Pt-喷他脒[(顺式-PtCl2)3(喷他脒)3][PtCl4]2和顺铂[顺式二氨基二氯铂(II)]与pUC8 DNA的结合率,以及这些铂化合物的结合对Bam HI、Hind III和Sal I限制性内切酶切割效率的影响。结果表明,在相同铂/核苷酸摩尔比下,DNA:Pt-喷他脒复合物中的共价DNA铂化作用比DNA:顺铂中的低12%至22%,并且与顺铂:DNA复合物相比,Pt-喷他脒:DNA复合物中与DNA结合的Pt-喷他脒分子数量显著更低。尽管两种化合物都抑制pUC8 DNA的Bam HI切割,但与顺铂相反,Pt-喷他脒并不阻止Hind III的切割活性。顺铂和Pt-喷他脒均不抑制Sal I的切割活性,其识别序列与Bam HI和Hind III位点相邻。

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