My PhD project
Activity: Other activity types › Other (prizes, external teaching and other activities) - Other
Ulrike Leurs - Participant
- Biostructural Research
Histone demethylation is one of the most interesting and ambigious histone modifications. As methylation does not alter the charge of the histone protein, it can result in both gene activation and repression. Lysine residues of histone proteins can be either methylated once, twice or three times; these different methylation states yield a considerable diversity in the possible biological outcome of this modification. The histone demethylases from the Jmj2C family have been linked to promotion of tumor growth, X-linked mental retardation and cleft lip palate. Therefore, these enzymes are considered oncogenes; their selective inhibition might be a possible therapeutic approach to treat cancer. However, the development of selective inhibitors appears to be difficult due to the high sequence and structure similarity within this protein family. The histone demethylase small-molecule inhibitors developed so far inhibit also other histone-modifying enzymes. A possible approach to overcome this problem would be the development of highly specific, targeted drugs. Such targeted drugs could consist of so called peptidomimetics coupled to small molecule inhibitors. The selectivity of these drugs would be promoted through the peptidomimetic part of the drug that imitates the enzyme substrate.
The overall goal of this project is to synthesize and biochemically characterize highly selective and potent inhibitors for histone demethylases from the Jmj2C family.
External organisation (Academic)
|Name||University of Copenhagen|
Research output: Contribution to journal › Journal article › Research › peer-review