Butyrolactone 3 is a selective inhibitor of histone acetyltransferase Gcn5 with affinity for the enzyme comparable to its natural substrate. Butyrolactone 3 is very useful tool in understanding and further studying the histone code.
ChEBI: (2S,3R)-4-methylene-5-oxo-2-propyl-3-oxolanecarboxylic acid is a gamma-lactone.
the analogs of butyrolactone 3 only showed a weak inhibition of cbp, while butyrolactone 3 led to an inhibition of gcn5. it was important to see that in the presence of acetyl-coa the kd value for binding of histone h3 to gcn5 or pcaf was around 100 mm. moreover, the affinity of butyrolactone 3 to the gcn5 enzyme was found to be comparable to that of the natural substrate h3 and could provide an good starting point for the study of sar. in addition, a nonirreversible inhibition of gcn5 could be determine, and thus a michael addition of nucleophilic groups of the enzymebs active side was unlikely. therefore, the derivatization of gbutyrolactone 3 at position 2 might be a promising starting point for future sar studies [1].
1. m. biel, a. kretsovali, e. karatzali, et al. design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase gcn5. angewandte chemie international edition 43, 3974-3976 (2004).
