title: Design, synthesis, photochemical properties and cytotoxic activities of water-soluble caged L-leucyl-L-leucine methyl esters that control apoptosis of immune cells.
abstract: L-Leucyl-L-leucine methyl esters (LeuLeuOMe) is a lysosomotropic agent that induces apoptosis of certain immune cells. Glucose-carrying 2-nitrobenzyl (2-NB) and 2-nitrophenethyl (2-NPE) caged LeuLeuOMe, 1a and b, were synthesized and their photochemical and immunological properties were studied. Caged glycine methyl esters (GlyOMe), 2a,b, were also prepared to examine the cytotoxic activity of the photolytic byproducts from 1a,b. All the caged compounds were soluble in PBS containing 1% DMSO more than 400 microM, and efficiently released the substrates upon irradiation at 350 nm. While both 1a and 1b were not toxic to HL60 cells, 1b released LeuLeuOMe more quickly and induced apoptosis of HL60 cells far more efficiently than 1a. Although GlyOMe was not cytotoxic, 2a and b were slightly toxic before and after irradiation almost to the similar extent. Therefore, the photolytic products from the caging groups appear to be not toxic to the cells, and the apoptosis inducing activity of 1a and b may be for the most part due to LeuLeuOMe.
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mizuta
authors.forename: Soichiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Furuta
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Michiko
authors.initials: M
authors.lastname: Iwamura
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D015195:Drug Design; D004355:Drug Stability; D005947:Glucose / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D010782:Photolysis; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000528:radiation effects; D012995:Solubility
chemical_list: D004151:Dipeptides; D011355:Prodrugs; C045139:leucyl-leucine-methyl ester; D005947:Glucose