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顺铂对聚(rG).聚(rC)修饰的生物物理研究。与复合物生物活性的关系。

Biophysical studies of the modification of poly(rG) . poly(rC) by cisplatin. Relations to the biological activity of the complex.

作者信息

Brabec V, Vrána O, Platonova G A, Kogan E M, Sidorova N S

机构信息

Institute of Biophysics, Czechoslovak Academy of Sciences, Brno.

出版信息

Chem Biol Interact. 1991;78(1):1-12. doi: 10.1016/0009-2797(91)90098-r.

DOI:10.1016/0009-2797(91)90098-r
PMID:2009577
Abstract

The integrity of the double-stranded complex polyriboguanylic.polyribocytidylic acid [poly(rG).poly(rC)] modified by antitumour cis-diamminedichloroplatinum(II)(cis-DDP) was studied with the aid of differential pulse polarography and terbium fluorescence measurement. The modification was made to level corresponding to rb = 0.05 (rb is defined as the number of platinum atoms covalently bound per one nucleotide residue). Two modes of the modification of the polynucleotide complex were employed: The action of cis-DDP on poly(G) before formation of the complex with poly(C) and on the complex already formed from non-modified polynucleotides. It was shown that in the latter case modification disordered the integrity of the complex only negligibly. while in the former case the modification resulted in a noticeably more extensive disturbance of the double-stranded polynucleotide complex. Moreover, the modification of the complex (after its formation) at rb = 0.02 led to improved interferon-inducing and antiviral activity of poly(rG).poly(rC) tested on mice infected by influenza virus. It was suggested that the combined effects of interferon-inducing and antiviral activities of poly(rG).poly(rC) and antiviral activity of cis-DDP may result in an increased effect over and above what may be expected from the actions of the two modalities separately.

摘要

借助微分脉冲极谱法和铽荧光测量法,研究了经抗肿瘤顺二氯二氨合铂(II)(顺铂)修饰的双链复合聚核糖鸟苷酸·聚核糖胞苷酸[聚(rG)·聚(rC)]的完整性。修饰达到rb = 0.05的水平(rb定义为每一个核苷酸残基共价结合的铂原子数)。采用了两种修饰多核苷酸复合物的方式:顺铂在与聚(C)形成复合物之前作用于聚(G),以及作用于由未修饰的多核苷酸已经形成的复合物。结果表明,在后一种情况下,修饰对复合物完整性的破坏微不足道,而在前一种情况下,修饰导致双链多核苷酸复合物受到更明显的广泛干扰。此外,在rb = 0.02时对复合物(形成后)进行修饰,提高了聚(rG)·聚(rC)对感染流感病毒的小鼠的干扰素诱导和抗病毒活性。有人提出,聚(rG)·聚(rC)的干扰素诱导和抗病毒活性与顺铂的抗病毒活性的联合作用可能会产生比单独两种方式作用预期更大的效果。

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