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

新型笼状化合物的开发和应用用于阐明免疫反应

• 批准号: 08680639
• 负责人: IWAMURA Michiko
• 金额: $ 1.34万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680639/
• 关键词: Caged compounds; Apoptosis; Immune responce; Cytotoxic activity; Sugar-modified 2-nitrobenzyil; Cell recognition; Macrophage; ケージド化合物; ロイシルロイシンメチルエステル; 糖を修飾したニトロベンジル基; マクロファージ系細胞株; 5-O-(β-Glucopyranosyl)-2-Nitrobenzyl

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.

亮氨酸甲酯是巨噬细胞和NK细胞的凋亡诱导剂，与葡萄糖修饰的2-硝基苯笼在含有1%DMSO的PBS中增加溶解度。以葡萄糖和5-羟基-2-硝基苯甲醛为原料，经过9步合成了5-0-（β -葡萄糖吡喃基）-2-硝基苯笼型Leu- Leu- ome 2a，溶度高达0.5 mM。在350nm照射下，它比2-硝基苯笼的Leu-Leu-OMe更有效地释放Leu-Leu-OMe并诱导HL60细胞凋亡。5-0- (β -glucopyranosyl) -2-nitrophenethyl笼型Leu-Leu-OMe 3释放底物速度更快，诱导HL60细胞凋亡的效果优于2a。期望利用它们的细胞识别能力，合成了乳糖、半乳糖和甘露糖修饰的2-硝基苯衍生物2b-d，并对其光化学和免疫活性进行了测试。为了利用巨噬细胞对含磷脂酰丝氨酸脂质体的吞噬功能，设计并合成了2-硝基苄基5-羟基上具有类固醇骨架的笼状Leu-Leu-OMe。5表现出令人满意的笼状化合物特性。

项目成果

Iwamura, M.et al.: "Acyloxycoumarinylmethyl-Caged cAMP,the Photolabile and Membrane-Permeable Derivative of cAMP" Biochem.Biophys.Res.Commun.228. 193-198 (1996)

Iwamura, M.等人：“酰氧基香豆素甲基笼状 cAMP，cAMP 的光不稳定且膜可渗透的衍生物”Biochem.Biophys.Res.Commun.228。

Furuta, T., Takeuchi, K.and Iwamura, M.: "Activation of selenoglycosides by photoinduced electron transfer." Chem.Commun.1996. 157-158 (1996)

Furuta, T.、Takeuchi, K. 和 Iwamura, M.：“通过光诱导电子转移激活硒代糖苷。”

Furuta,T., and Iwamura,M.: "New Caged Croups:7-Substituted Coumarinylmethyl Phosphate Esters." Methods in Enzymol.291. 50-63 (1998)

Furuta,T. 和 Iwamura,M.：“新笼养群体：7-取代香豆素甲基磷酸酯。”

Furuta,Momotake,Sugimoto,Torigai,Hatayama,IWAMURA: "Acyloxycouonarinyl methyl caged CAMP,the photalabile and Mombrane-Pelmeable Derivative of cAMP that stimulates Pigment-Dispeision Responce" Biochemical and Biophysical Research Commun.228. 193-198 (1996)

Furuta，Momotake，Sugimoto，Torigai，Hatayama，IWAMURA：“酰氧基香豆素甲基笼状 CAMP，刺激色素分散反应的 cAMP 的 photalabile 和 Mombrane-Pelmeable 衍生物”生化和生物物理研究 Commun.228。