D-Eritadenine
(Synonyms: 4-(6-氨基-9H-嘌呤-9-基)-4-脱氧-D-赤酮酸) 目录号 : GC40294An inhibitor of SAAH
Cas No.:23918-98-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
D-Eritadenine is an adenosine analog and a potent, reversible inhibitor of S-adenosylhomocysteine hydrolase (SAAH; IC50 = 7 nM). It inhibits growth of C. parvum parasites (MIC50 = 3 μM) without exhibiting cytotoxicity in HCT-8 cells (CC50 = >1 mM). Dietary administration of D-eritadenine (50 mg/kg) increases liver microsomal phosphatidylethanolamine concentration and decreases liver microsomal δ6 desaturase activity and plasma cholesterol levels in rats.
| Cas No. | 23918-98-1 | SDF | |
| 别名 | 4-(6-氨基-9H-嘌呤-9-基)-4-脱氧-D-赤酮酸 | ||
| Canonical SMILES | NC1=NC=NC2=C1N=CN2C[C@@H](O)[C@@H](O)C(O)=O | ||
| 分子式 | C9H11N5O4 | 分子量 | 253.2 |
| 溶解度 | 1N HCl: slightly soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.9494 mL | 19.7472 mL | 39.4945 mL |
| 5 mM | 0.7899 mL | 3.9494 mL | 7.8989 mL |
| 10 mM | 0.3949 mL | 1.9747 mL | 3.9494 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-Eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-Eritadenine
J Biol Chem 2002 Mar 1;277(9):7477-82.PMID:11741948DOI:10.1074/jbc.M109187200.
D-Eritadenine (DEA) is a potent inhibitor (IC(50) = 7 nm) of S-adenosyl-l-homocysteine hydrolase (AdoHcyase). Unlike cyclic sugar Ado analogue inhibitors, including mechanism-based inhibitors, DEA is an acyclic sugar Ado analogue, and the C2' and C3' have opposite chirality to those of the cyclic sugar Ado inhibitors. Crystal structures of DEA alone and in complex with AdoHcyase have been determined to elucidate the DEA binding scheme to AdoHcyase. The DEA-complexed structure has been analyzed by comparing it with two structures of AdoHcyase complexed with cyclic sugar Ado analogues. The DEA-complexed structure has a closed conformation, and the DEA is located near the bound NAD(+). However, a UV absorption measurement shows that DEA is not oxidized by the bound NAD(+), indicating that the open-closed conformational change of AdoHcyase is due to the substrate/inhibitor binding, not the oxidation state of the bound NAD. The adenine ring of DEA is recognized by four essential hydrogen bonds as observed in the cyclic sugar Ado complexes. The hydrogen bond network around the acyclic sugar moiety indicates that DEA is more tightly connected to the protein than the cyclic sugar Ado analogues. The C3'-H of DEA is pointed toward C4 of the bound NAD(+) (C3'...C4 = 3.7 A), suggesting some interaction between DEA and NAD(+). By placing DEA into the active site of the open structure, the major forces to stabilize the closed conformation of AdoHcyase are identified as the hydrogen bonds between the backbone of His-352 and the adenine ring, and the C3'-H...C4 interaction. DEA has been believed to be an inactivator of AdoHcyase, but this study indicates that DEA is a reversible inhibitor. On the basis of the complexed structure, selective inhibitors of AdoHcyase have been designed.
Efficacy of S-adenosylhomocysteine hydrolase inhibitors, D-Eritadenine and (S)-DHPA, against the growth of Cryptosporidium parvum in vitro
Exp Parasitol 2010 Oct;126(2):113-6.PMID:20412798DOI:10.1016/j.exppara.2010.04.007.
D-Eritadenine and (S)-DHPA are aliphatic adenosine analogues known to target S-adenosylhomocysteine hydrolase (SAHH) and potent antiviral compounds. In the present study, we demonstrate that these two compounds also display efficacy against recombinant SAHH enzyme of the protozoan parasite Cryptosporidium parvum, as well as inhibition of parasite growth in vitro. Our data confirm that SAHH could serve as a rational drug target in cryptosporidial infection and antiviral adenosine analogues are potential candidates for drug development against cryptosporidiosis.
The effect of aliphatic adenine analogues on S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase in intact rat hepatocytes
Mol Pharmacol 1984 Nov;26(3):553-8.PMID:6493210doi
The aliphatic adenine analogues, D-Eritadenine, L-eritadenine, L-threoeritadenine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)DHPA] function as inhibitors/inactivators of purified S-adenosylhomocysteine (AdoHcy) hydrolase, but these compounds did not induce reduction of enzyme-bound NAD+. D-Eritadenine, L-eritadenine, (S)DHPA, and L-threo-eritadenine inactivated AdoHcy hydrolase in hepatocytes, and the efficiency decreased in the order mentioned. Concurrently, there was an increase in the AdoHcy content. The accumulation of AdoHcy in the presence of (S)DHPA was more pronounced than would be expected from the inactivation of enzyme activity, suggesting that this compound may function as a reversible inhibitor as well. Furthermore, the inactivation of the intracellular enzyme by (S)DHPA is remarkable in the light of the fact that this compound induces no inactivation of purified AdoHcy hydrolase, but merely functions as an inhibitor of the enzyme. At low concentration of D-Eritadenine (less than 6 microM), a distinct lag period could be demonstrated before accumulation of AdoHcy occurred. This suggests that the AdoHcy hydrolase activity must be decreased below a certain level to cause an increase in cellular AdoHcy. None of the analogues tested completely inactivated AdoHcy hydrolase and a residual enzyme activity was observed. The adenosine deaminase inhibitor, 2'-deoxycoformycin, did not potentiate the effect of these compounds on AdoHcy catabolism. The inactive enzyme formed in the presence of aliphatic adenine analogues was not reactivated under conditions where the inactivation induced by 9-beta-D-arabinofuranosyladenine was reversible.
Structure and function of eritadenine and its 3-deaza analogues: potent inhibitors of S-adenosylhomocysteine hydrolase and hypocholesterolemic agents
Biochem Pharmacol 2007 Apr 1;73(7):981-9.PMID:17214973DOI:10.1016/j.bcp.2006.12.014.
D-Eritadenine (DEA) is a potent inhibitor of S-adenosyl-l-homocysteine hydrolase (SAHH) and has hypocholesterolemic activity. We have hypothesized that 3-deaza-DEA (C3-DEA) and its analogues retain high level of SAHH inhibitory activity and have resistance to deamination and glycosidic bond hydrolysis in vivo. Such C3-DEA analogues would have much higher hypocholesterolemic activity. C3-DEA, and its methyl ester (C3-OMeDEA) and its methyl amido (C3-NMeDEA) were synthesized to examine their SAHH inhibitory and hypocholesterolemic activities. A crystal structure of SAHH containing C3-DEA was determined and confirmed that DEA and C3-DEA bound to the same site of SAHH with the same binding mode. The SAHH inhibitory activities of C3-DEA (K(I)=1.5 microM) and C3-OMeDEA (K(I)=1.5 microM) are significantly lower than that of DEA (K(I)=30 nM), while rats fed by C3-DEA and C3-OMeDEA decrease the total plasma cholesterol and phospholipids by 36-40% and 23%, respectively, which is similar to the level of reductions (42% and 27%) by DEA. C3-NMeDEA lost most of the SAHH inhibitory activity (K(I)=30 microM) and dietary C3-NMeDEA does not decrease cholesterol and phospholipid in plasma but decreases the triacylglycerol level by 16%. DEA and C3-DEA analogues are neither substrates nor inhibitors of adenosine deaminase.
Characterization of S-adenosylhomocysteine hydrolase from Cryptosporidium parvum
FEMS Microbiol Lett 2007 Aug;273(1):87-95.PMID:17559404DOI:10.1111/j.1574-6968.2007.00795.x.
The S-adenosylhomocysteine hydrolase from the apicomplexan Cryptosporidium parvum (CpSAHH) has been characterized. CpSAHH is a single-copy, intronless gene of 1479 bp encoding a protein of 493 amino acids with a molecular mass of 55.6 kDa. Reverse transcriptase-polymerase chain reaction analysis confirmed that CpSAHH is expressed both in intracellular stages (in C. parvum-infected HCT-8 cells 24 h after infection) and in sporozoites. CpSAHH was expressed in Escherichia coli TB1 cells as a fusion with maltose-binding protein. The recombinant fusion was cleaved by Factor Xa and the enzymatic activity of both the fusion protein and the purified separated CpSAHH was measured. The enzymatic activity of CpSAHH was inhibited by D-Eritadenine, S-DHPA and Ara-A.