N2-Acetylguanine
目录号 : GC66325
N2-Acetylguanine 是一种 C2 修饰的鸟嘌呤。N2-Acetylguanine 与 GR（鸟嘌呤-鸟嘌呤核糖开关）结合，Kd 值为 300 nM。N2-Acetylguanine 调节转录终止。N2-乙酰鸟嘌呤具有抗菌药物的研究潜力。
Cas No.:19962-37-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N2-Acetylguanine is a C2-modified guanine. N2-Acetylguanine binds GR (guanine-guanine riboswitch) with an Kd value of 300 nM. N2-Acetylguanine modulate transcriptional termination. N2-Acetylguanine has the potential for the research of antimicrobial agent[1].
N2-Acetylguanine completely disrupt a key Watson-Crick pairing interaction between the ligand and RNA[1].
N2-Acetylguanine (20 µM) promotes transcriptional termination in Bacillus subtilis [1].
| Cas No. | 19962-37-9 | SDF | Download SDF |
| 分子式 | C7H7N5O2 | 分子量 | 193.16 |
| 溶解度 | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.1771 mL | 25.8853 mL | 51.7706 mL |
| 5 mM | 1.0354 mL | 5.1771 mL | 10.3541 mL |
| 10 mM | 0.5177 mL | 2.5885 mL | 5.1771 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。
High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch
Molecules 2020 May 13;25(10):2295.PMID:32414072DOI:10.3390/molecules25102295.
Riboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions. These studies have revealed compounds that have low to sub-micromolar affinity and, in a few cases, have antimicrobial activity. To further understand how these compounds interact with the guanine riboswitch, we have performed an integrated structural and functional analysis of representative guanine derivatives with modifications at the C8, C6 and C2 positions. Our data indicate that while modifications of guanine at the C6 position are generally unfavorable, modifications at the C8 and C2 positions yield compounds that rival guanine with respect to binding affinity. Surprisingly, C2-modified guanines such as N2-Acetylguanine completely disrupt a key Watson-Crick pairing interaction between the ligand and RNA. These compounds, which also modulate transcriptional termination as efficiently as guanine, open up a significant new chemical space of guanine modifications in the search for antimicrobial agents that target purine riboswitches.
Efficient synthesis of 2'-C-beta-methylguanosine
J Org Chem 2006 May 12;71(10):4018-20.PMID:16674089DOI:10.1021/jo0602165.
2'-beta-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2'-C-beta-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-d-ribofuranose (1) and N2-Acetylguanine, we obtained the title compound in two steps (78% overall yield) with high stereoselectivity (beta/alpha > 99:1) and high regioselectivity (N9/N7 > 99:1). Extension of this strategy to the classic synthesis of guanosine also resulted in high stereoselectivity (beta/alpha = 99:1) and improved regioselectivity (N9/N7 = 97:3).
Reactivity of haloketenes and halothioketenes with nucleobases: chemical characterization of reaction products
Chem Res Toxicol 1998 May;11(5):454-63.PMID:9585476DOI:10.1021/tx9701438.
Halothioketenes and haloketenes are postulated as intermediates in haloolefin bioactivation. Little is known about the interactions of these reactive intermediates with macromolecules such as DNA. DNA binding, however, may be relevant in the toxicity of the parent olefins since they or their proximate metabolites are genotoxic. This prompted us to elucidate the structures and properties of potential DNA adducts formed. Adenine, cytosine, guanine, and thymine were reacted with chloro- and dichlorothioketene, chloro- and dichloroketene, and chloro- and dichloroacyl chloride. While thymine did not react, adenine and cytosine formed stable DNA base adducts with all reaction partners as demonstrated by HPLC analysis. Guanine yielded only products with chloroketene and chloroacetyl chloride. The pH-dependent UV spectra, 1H and 13C NMR, FT-IR, and elemental analysis showed (i) nucleophilic attack of the exocyclic amino groups of the DNA bases yielded haloacyl (thio)amides with all reactants as clearly demonstrated by the FT-IR spectra; (ii) the sulfur in the initial thioamides seems to be rapidly exchanged with oxygen; (iii) the acyl chlorides form identical products but in lower yields as compared to the haloketenes. Reactions of the nucleosides with haloketenes showed the formation of similar nucleoside adducts upon HPLC and MS analysis. Beside the modification of the base moieties, additional peaks in the reaction mixtures analyzed suggested acylation of the deoxyribose hydroxyl groups. In aqueous solutions at pH 7 N6-(chloroacetyl)adenine, N4-(chloroacetyl)cytosine, and N2-(chloroacetyl)guanine are not stable and cleaved to the original base or form 1,N6-acetyladenine, 3,N4-acetylcytosine, 1,N2-Acetylguanine, and N2,3-acetylguanine. Under the same conditions, N6-(dichloroacetyl)adenine and N4-(dichloroacetyl)cytosine were completely hydrolyzed to adenine and cytosine, respectively. All haloacyl DNA base adducts proved to be stable at pH 5 but were rapidly degraded at neutral or alkaline pH. The compounds with an additional five-membered ring remained unchanged after 1 week at room temperature. All synthesized DNA base adducts except N2-(chloroacetyl)guanine and 1,N2-Acetylguanine were fluorescent. The characterized compounds, especially the etheno (epsilon) base adduct-related derivatives, may represent potential DNA adducts formed as a consequence of haloolefin bioactivation.
Synthesis and biological evaluation of acyclic neplanocin analogues
J Med Chem 1987 Jan;30(1):198-200.PMID:3027333DOI:10.1021/jm00384a033.
Acyclic neplanocin analogues were prepared by condensation of adenine or N2-Acetylguanine with (E)-1,4-dichlorobut-2-ene and subsequent hydrolysis. The N-9-substituted product 9-[(E)-4-hydroxybut-2-enyl]adenine was obtained when adenine was employed as the starting purine, while N2-Acetylguanine yielded both the N-7 and N-9 isomers. Cell-culture studies revealed that only the chloro-substituted intermediate 9-[(E)-4-chlorobut-2-enyl]adenine exhibited significant cytotoxicity against P-388 mouse lymphoid leukemia cells, while the N-9-substituted guanine analogue 9-[(E)-4-hydroxybut-2-enyl]guanine inhibited replication of herpes simplex viruses type 1 and type 2.
Metabolism of O6-benzylguanine, an inactivator of O6-alkylguanine-DNA alkyltransferase
Cancer Res 1994 Oct 1;54(19):5123-30.PMID:7923129doi
O6-Benzylguanine effectively inactivates the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, leading to an increase in the therapeutic index of 1,3-bis(2-chloroethyl)-1-nitrosourea in nude mouse xenograft studies. To investigate the fate of this inactivator in mammalian systems, we examined its biodistribution and metabolism following i.p. administration of 8-[3H]-O6-benzylguanine to male Sprague-Dawley rats and BALB/c mice. Following administration to rats, there were significantly higher levels of radioactivity in liver than in lung, spleen, kidney, small intestine, and esophagus for up to 24 h. Major urinary metabolites were identified as O6-benzyl-7,8-dihydro-8-oxoguanine, N2-acetyl-O6-benzylguanine, and N2-acetyl-O6-benzyl-7,8-dihydro-8-oxoguanine. Debenzylated metabolites included guanine, 7,8-dihydro-8-oxoguanine, and N2-Acetylguanine. In contrast to rat metabolism, acetylated derivatives were not found in mouse urine. However, O6-benzyl-7,8-dihydro-8-oxoguanine was a major metabolite in the mouse. O6-Benzyl-7,8-dihydro-8-oxoguanine was a very effective O6-alkylguanine-DNA alkyltransferase inactivator and exhibited a 50% effective dose in HT29 cell extracts of 0.3 microM compared to 0.2 microM for O6-benzylguanine. The O6-alkylguanine-DNA alkyltransferase depleting activity of N2-acetyl-O6-benzylguanine and N2-acetyl-O6-benzyl-7,8-dihydro-8-oxoguanine were, respectively, 120- and 325-fold lower than O6-benzylguanine in HT29 cell-free extracts.