Journal article

Formaldehyde-activated WEHI-150 induces DNA interstrand crosslinks with unique structural features

Paul P Pumuye, Benny J Evison, Shyam K Konda, J Grant Collins, Celine Kelso, Jelena Medan, Brad E Sleebs, Keith Watson, Don R Phillips, Suzanne M Cutts

Bioorganic & Medicinal Chemistry | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2020


Mitoxantrone is an anticancer anthracenedione that can be activated by formaldehyde to generate covalent drug-DNA adducts. Despite their covalent nature, these DNA lesions are relatively labile. It was recently established that analogues of mitoxantrone featuring extended side-chains terminating in primary amino groups typically yielded high levels of stable DNA adducts following their activation by formaldehyde. In this study we describe the DNA sequence-specific binding properties of the mitoxantrone analogue WEHI-150 which is the first anthracenedione to form apparent DNA crosslinks mediated by formaldehyde. The utility of this compound lies in the versatility of the covalent binding mode..

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University of Melbourne Researchers