Methods for Elucidation of DNA-Anticancer Drug Interactions and Their Applications in the Development of New Drugs

Majus Misiak; Francesco Mantegazza; Giovanni Beretta

doi:10.2174/1381612822666160831114622

Methods for Elucidation of DNA-Anticancer Drug Interactions and Their Applications in the Development of New Drugs

Abstract

DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration is associated with adverse side effects, whereas the inherent genotoxicity of these drugs is associated with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and at the same would characterize with improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure and what is their significance for the antitumor activity. Based on this knowledge we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug-DNA interaction and aid in the development of new drugs.

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Authors (3)

Majus Misiak
Francesco Mantegazza
- School of Medicine Universita' di Milano - Bicocca. Milan, Italy
Giovanni Beretta
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano. Milan, Italy Department of Experimental Oncology and Molecular Medicine

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Category:: Articles
Type:: artykuł w czasopiśmie wyróżnionym w JCR
Published in:: CURRENT PHARMACEUTICAL DESIGN no. 22, edition 46, pages 1 - 16,
ISSN: 1381-6128
Language:: English
Publication year:: 2016
Bibliographic description:: Misiak M., Mantegazza F., Beretta G.: Methods for Elucidation of DNA-Anticancer Drug Interactions and Their Applications in the Development of New Drugs// CURRENT PHARMACEUTICAL DESIGN. -Vol. 22, iss. 46 (2016), s.1-16
DOI:: Digital Object Identifier (open in new tab) 10.2174/1381612822666160831114622
Verified by:: Gdańsk University of Technology