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Issue 43, 2016
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Isolation and structural analysis of the covalent adduct formed between a bis-amino mitoxantrone analogue and DNA: a pathway to major–minor groove cross-linked adducts

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Abstract

The major covalent adduct formed between a 13C-labelled formaldehyde activated bis-amino mitoxantrone analogue (WEHI-150) and the hexanucleotide d(CG5MeCGCG)2 has been isolated by HPLC chromatography and the structure determined by NMR spectroscopy. The results indicate that WEHI-150 forms one covalent bond through a primary amine to the N-2 of the G2 residue, with the polycyclic ring structure intercalated at the 5MeC3pG4/G10p5MeC9 site. Furthermore, the WEHI-150 aromatic ring system is oriented approximately parallel to the long axis of the base pairs, with one aliphatic side-chain in the major groove and the other side-chain in the minor groove. This study indicates that mitoxantrone derivatives like WEHI-150 should be capable of forming major–minor groove cross-linked adducts that will likely produce considerably different intracellular biological properties compared to known anthracycline and anthracenedione anticancer drugs.

Graphical abstract: Isolation and structural analysis of the covalent adduct formed between a bis-amino mitoxantrone analogue and DNA: a pathway to major–minor groove cross-linked adducts

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Publication details

The article was received on 24 Aug 2016, accepted on 07 Oct 2016 and first published on 07 Oct 2016


Article type: Paper
DOI: 10.1039/C6OB02100J
Citation: Org. Biomol. Chem., 2016,14, 10217-10221
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    Isolation and structural analysis of the covalent adduct formed between a bis-amino mitoxantrone analogue and DNA: a pathway to major–minor groove cross-linked adducts

    S. K. Konda, C. Kelso, J. Medan, B. E. Sleebs, D. R. Phillips, S. M. Cutts and J. G. Collins, Org. Biomol. Chem., 2016, 14, 10217
    DOI: 10.1039/C6OB02100J

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