OleD Loki as a Catalyst for Hydroxamate Glycosylation

This research explores using a specific enzyme, OleD Loki, to modify histone deacetylase (HDAC) inhibitors by attaching sugar molecules (glycosylation). This modification process is evaluated for its effects on the inhibitors' ability to kill cancer cells. The study also investigates how glycosylation affects the chemical stability of these inhibitors and their impact on tissue regeneration in axolotl embryos. Computational models are used to predict how well the enzyme interacts with different HDAC inhibitors, suggesting that some inhibitors might bind in a way that prevents the enzyme from working effectively.

• 1
  OleD Loki can convert a wide range of HDAC inhibitors into their corresponding hydroxamate glycosyl esters.
• 2
  Glucosylation generally decreases the cytotoxicity of the HDAC inhibitors by 20- to > 3000-fold.
• 3
  Computational models suggest that certain HDACis may form unproductive, potentially inhibitory, complexes with GTs.