3-Deaza-腺苷

3-Deaza-腺苷用途

3-Deazaadenosine 是一种 S-腺苷高半胱氨酸水解酶 (S-adenosylhomocysteine hydrolase) 抑制剂,Ki 值为 3.9 µM；3-Deazaadenosine 具有抗炎、抗增殖、抗 HIV 等活性。

3-Deaza-腺苷名称

[ CAS 号 ]:
6736-58-9

[ 中文名 ]:
4-氨基-1-BETA-D-呋喃核糖基-1H-咪唑并[4,5-C]吡啶

[ 英文名 ]:
3-Deazaadenosine

[中文别名 ]:

3-氮杂腺苷

[英文别名 ]:

C3-Ado
3-Deaza-D-adenosine
3-DEAZAADENOSINE

3-Deaza-腺苷生物活性

[ 描述 ]:

3-Deazaadenosine 是一种 S-腺苷高半胱氨酸水解酶 (S-adenosylhomocysteine hydrolase) 抑制剂,Ki 值为 3.9 µM；3-Deazaadenosine 具有抗炎、抗增殖、抗 HIV 等活性。

[ 相关类别 ]:

信号通路 >> 抗感染 >> HIV

研究领域 >> 炎症/免疫

研究领域 >> 感染

[ 靶点 ]

IC50: 0.15 (HIV-1, A012 isolate), 0.20 µM (HIV-1, A018 isolate)[1] Ki: 3.9 µM (S-adenosylhomocysteine hydrolase)[1]

[体外研究]

3-Deazaadenosine是S-腺苷高半胱氨酸水解酶的抑制剂,Ki为3.9μM。 3-Deazaadenosine显示抗HIV效应,并抑制感染HIV-1分离株(A012和A018)的外周血单核细胞(PBMCs)中的p24抗原,IC50分别为0.15和0.20μM[1]。 3-Deazaadenosine(1-100μM)抑制LPS诱导的TNF-αmRNA表达,增加NF-κB的DNA结合活性,并引起RAW264.7细胞中IκBα的蛋白水解降解,但不引起IκBβ的蛋白水解降解。 3-Deazaadenosine(100μM)增强NF-κB的核转位,但阻断LPS诱导的NF-κB转录活性,并且这种抑制通过添加同型半胱氨酸而得到增强[2]。 3-Deazaadenosine(50,100μM)剂量依赖性地抑制Raf和ERK,蛋白质依赖性激酶1,蛋白激酶B(Akt)和叉头转录因子FoxO1a的磷酸化。 3-Deazaadenosine(50μM)通过干扰Ras信号传导抑制血管平滑肌细胞(VSMC)增殖[3]。

[细胞实验]

HIV-1菌株A012和A018用于测定。测量p24抗原的抑制。简而言之，将PHA刺激的外周血单核细胞（PBMC）与HIV-1株在37℃下孵育1小时，每2×105个PBMC细胞50％组织培养感染剂量（TCID50）的病毒原种200倍。。 TCID50定义为50％接种孔为阳性的病毒库存量。然后使细胞在具有不同药物浓度的微量滴定板中以每孔2×10 5个细胞生长。在第4天，将细胞重新悬浮并用新鲜培养基和3-脱氮腺苷1：3分开。在第7天通过ELISA测定上清液p24抗原[1]。

[参考文献]

[1]. Gordon RK, et al. Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners. Eur J Biochem. 2003 Sep;270(17):3507-17.

[2]. Jeong SY, et al. 3-deazaadenosine, a S-adenosylhomocysteine hydrolase inhibitor, has dual effects on NF-kappaB regulation. Inhibition of NF-kappaB transcriptional activity and promotion of IkappaBalpha degradation. J Biol Chem. 1999 Jul 2;274(27):18981-8.

[3]. Sedding DG, et al. 3-Deazaadenosine prevents smooth muscle cell proliferation and neointima formation by interfering with Ras signaling. Circ Res. 2009 May 22;104(10):1192-200.

[相关活性小分子]

3-Deaza-腺苷物理化学性质

[ 密度 ]:
1.9±0.1 g/cm3

[ 沸点 ]:
665.7±65.0 °C at 760 mmHg

[ 熔点 ]:
228-229ºC

[ 分子式 ]:
C₁₁H₁₄N₄O₄

[ 分子量 ]:
266.253

[ 闪点 ]:
356.4±34.3 °C

[ 精确质量 ]:
266.101501

[ PSA ]:
126.65000

[ LogP ]:
0.18

[ 外观性状 ]:
白色至类白色固体

[ 蒸汽压 ]:
0.0±2.1 mmHg at 25°C

[ 折射率 ]:
1.834

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
H2O: 10 mg/mL with heating to 60 °C

3-Deaza-腺苷安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 安全声明 (欧洲) ]:
24/25

[ 危险品运输编码 ]:
UN 2811

[ WGK德国 ]:
3

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

3-Deaza-腺苷合成路线

详细合成路线

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3-Deaza-腺苷文献

Disruption of choline methyl group donation for phosphatidylethanolamine methylation in hepatocarcinoma cells.

J. Biol. Chem. 277(19) , 17217-25, (2002)

Despite being widely hypothesized, the actual contribution of choline as a methyl source for phosphatidylethanolamine (PE) methylation has never been demonstrated, mainly due to the inability of conve...

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction.

Exp. Mol. Med. 33(4) , 284-92, (2001)

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the...

Identification of A-minor tertiary interactions within a bacterial group I intron active site by 3-deazaadenosine interference mapping.

Biochemistry 41(33) , 10426-38, (2002)

The A-minor motifs appear to be the most ubiquitous helix packing elements within RNA tertiary structures. These motifs have been identified throughout the ribosome and almost every other tertiary-fol...

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