Substitution-Inert Polynuclear Platinum Complexes with Dangling Amines: Condensation/Aggregation of Nucleic Acids and Inhibition of DNA-Related Enzymatic Activities

0510161 - BFÚ 2020 US eng J - Journal Article
Malina, Jaroslav - Čechová, Klára - Farrell, N.P. - Brabec, Viktor
Substitution-Inert Polynuclear Platinum Complexes with Dangling Amines: Condensation/Aggregation of Nucleic Acids and Inhibition of DNA-Related Enzymatic Activities.
Inorganic Chemistry. Roč. 58, č. 10 (2019), s. 6804-6810. ISSN 0020-1669. E-ISSN 1520-510X
Keywords : transcriptional activity * topoisomerase-i * phosphate clamp * molecules * enhancement
Impact factor: 4.825, year: 2019
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acs.inorgchem.9b00254

The substitution-inert polynuclear platinum complexes (SI-PPCs) are now recognized as a distinct subclass of platinum anticancer drugs with high DNA binding affinity. Here, we investigate the effects of SI-PPCs containing dangling amine groups in place of NH3 as ligands to increase the length of the molecule and therefore overall charge and its distribution. The results obtained with the aid of biophysical techniques, such as total intensity light scattering, gel electrophoresis, and atomic force microscopy, show that addition of dangling amine groups considerably augments the ability of SI-PPCs to condense/aggregate nucleic acids. Moreover, this enhanced capability of SI-PPCs correlates with their heightened efficiency to inhibit DNA-related enzymatic activities, such as those connected with DNA transcription, catalysis of DNA relaxation by DNA topoisomerase I, and DNA synthesis catalyzed by Taq DNA polymerase. Thus, the addition of the dangling amine groups resulting in structures of SI-PPCs, which differ so markedly from the derivatives of cisplatin used in the clinic, appears to contribute to the overall biological activity of these molecules.
Permanent Link: http://hdl.handle.net/11104/0300706