Synthesis, photoreactivity and cytotoxic activity of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer.
L-Leucyl-L-leucine methyl ester (Leu-Leu-OMe), an apoptosis inducer in natural killer cells and macrophages, was caged with trans-o-hydroxycinnamoyl (3a-d), trans-o-mercaptocinnamoyl (4) and o-nitrobenzyl derivatives (5a, b), and the photochemical reactivity of these derivatives in phosphate-buffered saline containing 1% dimethyl sulfoxide and their immunological properties were studied. All of the derivatives exhibited absorption at wavelengths longer than the UVB region. Although 3a-d and 4 were expected to isomerize to a cis isomer, which then cyclizes intramolecularly to give Leu-Leu-OMe and a coumarin derivative, cyclization efficiency was not satisfactory except for 3a. However, 3a itself caused necrosis (cell swelling) of U937 cells (a myeloid cell line). In contrast, 5a and b released Leu-Le-OMe quickly and efficiently and did not affect U937 cells. Although irradiated 5b induced necrosis, irradiated 3a and 5a induced apoptosis in these cells, as evidenced by a decrease in cell size.
Odaka
M
M
Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.
Furuta
T
T
Kobayashi
Y
Y
Iwamura
M
M
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000528:radiation effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D010777:Photochemistry
D004151:Dipeptides; C045139:leucyl-leucine-methyl ester