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
- Author(s)
- Konda, SK; Kelso, C; Medan, J; Sleebs, BE; Phillips, DR; Cutts, SM; Collins, JG;
- Details
- Publication Year 2016-11-02,Volume 14,Issue #43,Page 10217-10221
- Journal Title
- Org Biomol Chem
- Publication Type
- Journal Article
- 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.
- Publisher
- RSC
- Research Division(s)
- Chemical Biology
- PubMed ID
- 27735959
- Publisher's Version
- https://doi.org/10.1039/c6ob02100j
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-05-26 03:11:43
Last Modified: 2017-05-26 03:33:49