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Synthesis, Photoreactivity and Cytotoxic Activity of Caged Compounds of L‐Leucyl‐L‐Leucine Methyl Ester, an Apoptosis Inducer
Author(s) -
Odaka Mitsuyo,
Furuta Toshiaki,
Kobayashi Yoshiro,
Iwamura Michiko
Publication year - 1996
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1996.tb09633.x
Subject(s) - chemistry , inducer , apoptosis , u937 cell , stereoselectivity , stereochemistry , dimethyl sulfoxide , cytotoxic t cell , cell culture , reactivity (psychology) , medicinal chemistry , biochemistry , in vitro , organic chemistry , biology , gene , genetics , medicine , alternative medicine , catalysis , pathology
I,‐Leucyl‐L‐leucine methyl ester (Leu‐Leu‐OMe), an apoptosis inducer in natural killer cells and macro‐phages, was caged with trans ‐o‐hydroxycinnamoyl (3ad), 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 absorplion at wavelengths longer than the UVB region. Although 3a–d and 4 were expected to isomerize to a cis isomer, which thgn 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‐Leu‐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.