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Effect of microwave irradiation on covalent ligand-DNA interactions.

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  • Chemistry
  • Medicine


b902357g 2875..2877 Effect of microwave irradiation on covalent ligand–DNA interactionsw Khondaker M. Rahman and David E. Thurston* Received (in Cambridge, UK) 4th February 2009, Accepted 9th March 2009 First published as an Advance Article on the web 3rd April 2009 DOI: 10.1039/b902357g A 30 second burst of microwave irradiation at an energy level insufficient to cause DNA denaturation or damage drives the covalent reaction between pyrrolobenzodiazepine (PBD) antitumour agents and double-stranded or hairpin oligonucleotides to completion, a process that normally takes between 3–24 hours and thus offering the opportunity for higher-throughput screening of covalent-binding DNA-interactive agents. Microwave irradiation is known to increase the rate of different types of chemical reactions and is widely used to promote carbon–carbon and carbon–heteroatom bond formation.1 However, the effect of microwaves on ligand– macromolecule covalent interactions has not been previously investigated, although there are reports of microwave-accelerated biochemical fluorescence assay procedures.2 One reason why microwave irradiation has not been extensively investigated for accelerating biochemical interactions is that the high temperature typically associated with microwaves is widely assumed to be deleterious to macromolecules, leading to denaturation.3–5 However, we have found that by using short bursts of microwave irradiation at energy levels that do not cause significant heating of ligand–DNA mixtures or denaturation of annealed DNA duplexes, the rate of covalent binding of pyrrolobenzodiazepine (PBD) agents to DNA can be enhanced by up to B360-fold. The pyrrolobenzodiazepines (PBDs) are sequence-selective minor-groove binding molecules (Fig. 1A) which react covalently via their C11-position with the C2-NH2 functionalities of guanines with 1 : 1 stoichiometry (Fig. 1B). This study was carried out using three different types of pyrrolobenzodiaz

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