Synthesis of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer, and their cytotoxic activity.

In this study, we newly synthesized caged compounds of L-leucyl-L-leucine methyl ester and examined their photochemical and immunological properties. From the viewpoints of solubility in phosphate-buffered saline containing 1% dimethyl sulfoxide as well as photoreactivity, we chose two caged compounds, 1 and 2, for study. Upon irradiation, L-leucyl-L-leucine methyl ester with a trans-o-hydroxycinnamoyl group (1) releases L-leucyl-L-leucine methyl ester quite slowly, whereas L-leucyl-L-leucine methyl ester with an o-nitrobenzyl group (2) releases L-leucyl-L-leucine methyl ester quickly. Both irradiated compounds induced apoptosis of U937 cells, as evidenced by a decrease in cell size, although 1 itself caused necrosis (cell swelling) of these cells.