Development and application of novel caged compounds for clucidation of immune responce

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Leucyl-leucine methyl ester, known as an apoptosis inducer to macrophages and NK cells, was caged with glucose modified 2-nitrobenzyl to increase solubility in PBS containing 1%DMSO.5-0-(beta-glucopyranosyl)-2-nitrobenzyl caged Leu- Leu-OMe 2a, soluble as high as 0.5 mM,was synthesized through 9 steps using glucose and 5-hydroxy-2-nitro benzaldehyde as starting materials. Upon irradiation at 350nm, it released Leu-Leu-OMe and induced apoptosis to HL60 cells more effectively than 2-nitrobenzyl caged Leu-Leu-OMe. 5-0- (beta-glucopyranosyl) -2-nitrophenethyl caged Leu-Leu-OMe 3 was found to release the substrate more quickly and induce apoptosis of HL60 cells more effectively than 2a. an expectation of using their cell recognition abilities, lactose, galactose and mannose modified 2-nitrobenzyl derivatives 2b-d were synthesized and their photochemical as well as immunological activities were tested.A caged Leu-Leu-OMe having a steroid skeleton at 5-hydroxyl of 2-nitrobenzyl 5 was designed and synthesized in an attempt to make use of the phagocytosis function of macrophages towards phosphatidylserine containing liposomes. 5 showed satisfactory characteristics as a caged compound.