Modulation of relaxation activity of human topoisomerases by Pt(II)-based complexes.

Odra Pinato, Anna Benettazzo, Lisa Dalla Via, Nicholas P Farrell, Claudia Sissi

Journal of inorganic biochemistry 2020 Oct

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The clinical efficiency of Pt(II)-based drugs is founded on articulate mechanisms of action. Indeed it depends on a balanced combination of metal ion reactivity towards proteins and nucleic acids. Here we analysed the effect of two trans-platinum planar amines in comparison to cisplatin and transplatin on the DNA processivity by human topoisomerases I and IIα. Each tested metal complex produces DNA adducts with unique geometrical features and, consistently, they exert different effects on the activity of tested enzymes. Moreover, our results highlighted more subtle consequences on the enzymatic activity by the tested metal complexes which derive from a combination of preferential DNA or protein platination. Moreover, we observed that it is not possible to predict the overall output based only on the cis- vs trans- geometry of the tested metal complexes. This variable behaviour reflects the chemical reactivity profile of each single metal complex and can be usefully addressed to describe their different properties in the complex physiological environment. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Odra Pinato, Anna Benettazzo, Lisa Dalla Via, Nicholas P Farrell, Claudia Sissi. Modulation of relaxation activity of human topoisomerases by Pt(II)-based complexes. Journal of inorganic biochemistry. 2020 Oct;211:111178