N⁶-methyladenosine | 1867-73-8

• 物质功能分类: 生物化工 - 核酸类
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-methyladenosine
• 英文别名: N-methyladenosine；6-N-methyladenosine；(6-methyl)adenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol；N⁶-methyladenosin；N6‑methyladenosine；N6–Me-adenosine；m⁶A；NSC 29409；N6-Methyladenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(methylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 1867-73-8
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: VQAYFKKCNSOZKM-IOSLPCCCSA-N

物化性质

• 熔点：
  172 °C
• 沸点：
  649.1±65.0 °C(Predicted)
• 密度：
  1.85±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热、超声处理）
• 最大波长(λmax)：
  262 (pH 1)；266 (pH 7)
• 物理描述：
  Solid
• 碰撞截面：
  170.4 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

N6-甲基腺苷（m6A、NSC-29409、6-甲基腺苷、N-甲基腺苷）是一种碱基修饰的腺苷类似物，在天然RNA中作为稀有核苷。在mRNA中，N6-甲基腺苷（m6A）是第五种碱基。

靶点

Human Endogenous Metabolite

体外研究

N6-甲基腺苷是一种丰富的碱基修饰的腺苷类似物，在一些病毒和大多数真核生物中被发现，包括哺乳动物、昆虫、植物和酵母。它还存在于tRNA、rRNA、小核RNA（snRNA）以及某些长链非编码RNA，如Xist中。N6-甲基腺苷是转运核糖核酸(tRNA)降解的一种内源性尿苷产物。在许多组织中广泛存在，特别是在大脑中水平较高。N6-甲基腺苷在小鼠和人类mRNAs的终止密码子附近及3’UTRs内部富集。近期研究发现FTO，一个肥胖风险基因，编码m6A去甲基酶，而m6A是调节重要生理学过程的关键因素。

体内研究

LD50：小鼠灌胃大于1克/千克。

反应信息

• 作为反应物：
  描述：

  N⁶-methyladenosine 在 盐酸 作用下， 生成 6-甲基腺素
  参考文献：
  名称：

  Fujii, Tozo; Saito, Tohru, Heterocycles, 1982, vol. 17, p. 117 - 123

  摘要：

  DOI：
• 作为产物：
  描述：

  6-甲基腺素 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 16.08h， 生成 N⁶-methyladenosine
  参考文献：
  名称：

  High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries

  摘要：

  [GRAPHICS]The Vorbruggen glycosylation reaction was adapted into a one-step 5 min/130 degrees C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl triflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.

  DOI：

  10.1021/jo061885l

文献信息

• [EN] BIOACTIVE CONJUGATES FOR OLIGONUCLEOTIDE DELIVERY<br/>[FR] CONJUGUÉS BIOACTIFS POUR L'ADMINISTRATION D'OLIGONUCLÉOTIDES
  申请人：UNIV MASSACHUSETTS

  公开号：WO2017030973A1

  公开（公告）日：2017-02-23

  Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

  本文提供的自递送寡核苷酸具有高效的RISC进入、最小的免疫反应和非靶效应、无需配方的高效细胞摄取，以及高效和特异的组织分布。
• Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth-Generation by Prebiotic Methylations and Carbamoylations
  作者：Christina Schneider、Sidney Becker、Hidenori Okamura、Antony Crisp、Tynchtyk Amatov、Michael Stadlmeier、Thomas Carell

  DOI：10.1002/anie.201801919

  日期：2018.5.14

  prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here

  RNA世界假说假设地球上的生命始于催化其自身形成的小RNA分子。对该假设至关重要的是，需要针对RNA的益生元途径。然而，当代RNA不仅由四个规范的核碱基（A，C，G和U）构建，而且还包含许多化学修饰的（非规范）碱基。一个尚待解决的问题是，当生命需要更高的功能多样性（生物起源）时，这些非规范碱基是否与规范碱基（化学起源）平行或更晚地形成。在这里，我们显示异氰酸酯与亚硝酸钠的组合建立了与地球早期条件相容的甲基化和氨基甲酰化反应性。这些反应导致仍然存在的甲基化和氨基酸修饰的核苷的形成。
• NUCLEIC ACID OF FORMULA (I): GlXmGn, OR (II): ClXmCn, IN PARTICULAR AS AN IMMUNE-STIMULATING AGENT/ADJUVANT
  申请人：CureVac AG

  公开号：US20200016264A1

  公开（公告）日：2020-01-16

  The present invention relates to a nucleic acid of the general formula (I): G l X m G n , or (II): C l X m C n , which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.

  本发明涉及一般式(I)：G l X m G n 或(II)：C l X m C n的核酸，该核酸可以通过脂质进行修饰。本发明的核酸作为免疫刺激剂，诱导先天免疫应答。本发明还涉及一种药物组合物（在第一实施例中），每种组合物包含本发明的免疫刺激剂与药用活性载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）的组合。在另一实施例中，创新的核酸与至少一种药用活性成分、药用可接受的载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）结合。因此，本发明涉及一种疫苗，该疫苗对应于本发明的药物组合物（第二实施例），其中药用活性成分诱导特异免疫应答（例如抗原）。本发明同样涉及利用本发明的核酸或药物组合物治疗传染病、自身免疫疾病、过敏或癌症疾病。
• [EN] BINDING-SITE MODIFIED LECTINS AND USES THEREOF<br/>[FR] LECTINES DE SITE DE LIAISON MODIFIÉES ET USAGE CORRESPONDANT
  申请人：SMARTCELLS INC

  公开号：WO2010088261A1

  公开（公告）日：2010-08-05

  In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

  在一个方面，该公开提供了包括多价凝集素的交联材料，其中该多价凝集素具有至少两个葡萄糖结合位点，其中该凝集素包括至少一个与亲和配体共价连接的亲和配体，该亲和配体能够与至少一个所述结合位点中的葡萄糖竞争结合；以及包括绑定到共轭框架的两个或更多个独立亲和配体的共轭物，其中这两个或更多个亲和配体与葡萄糖在所述结合位点上与凝集素竞争结合，其中由于不同共轭物上的凝集素和亲和配体之间的非共价相互作用，共轭物在材料内交联。这些材料旨在根据所需葡萄糖浓度释放共轭物的量。根据最终应用，在各种实施例中，共轭物还可以包括药物和/或可检测标记。
• Compounds for modulating RNA interference
  申请人：——

  公开号：US20040204420A1

  公开（公告）日：2004-10-14

  The present invention pertains to compounds effective at modulating (inhibiting or enhancing) RNA interference in a cell or organism. Featured compounds are set forth and exemplified herein. Therapeutic methods and pharmaceutical compositions featuring the compounds are also provided. The invention further pertains to knock-out or knock-down cells and organisms including the compounds, and methods of analysis of gene expression profiles and proteomes.

  本发明涉及一种在细胞或生物体中调节（抑制或增强）RNA干扰的有效化合物。所述的特定化合物在此处列出并且进行了示范。还提供了以这些化合物为特色的治疗方法和药物组合物。该发明还涉及包括这些化合物的敲除或敲低细胞和生物体，以及基因表达谱和蛋白质组的分析方法。

表征谱图