Leiden Institute of Chemistry,
2333 CC Leiden
Doxorubicin is part of the anthracycline class of chemotherapeutics. Their main mechanism of action was considered to be DNA double-strand breakage, leading to cell death. Recent experiments with GFP-tagged histones have shown that these compounds are able to kick out histones (including their post-translational modifications). For aclarubicin, this is the actual dominant mechanism instead.
An array of (oligo)-saccharides related to doxorubicin and aclarubicin will be synthesized through a shuffleable building-block approach. Combined with a cell-biology and bio-informatics pipeline, these compounds will be tested for their effectiveness and side-effects, as well as their potential as epigenetic modifiers.