[(2R,3S,4R,5R)-5-[6-(6-氨基己基氨基)嘌呤-9-基]-3,4-二羟基四氢呋喃-2-基]磷酸二氢甲酯 | 38198-98-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: [(2R,3S,4R,5R)-5-[6-(6-氨基己基氨基)嘌呤-9-基]-3,4-二羟基四氢呋喃-2-基]磷酸二氢甲酯
• 英文名称: N⁶-(6-aminohexyl)-AMP
• 英文别名: N⁶-(6-amino-hexyl)-[5']adenylic acid；N(6)-Aminohexyladenosine monophosphate；[(2R,3S,4R,5R)-5-[6-(6-aminohexylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 38198-98-0
• 化学式: C₁₆H₂₇N₆O₇P
• 分子量: 446.4
• InChiKey: MIMJOEOVYXMMPO-XNIJJKJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  198
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [(2R,3S,4R,5R)-5-[6-(6-氨基己基氨基)嘌呤-9-基]-3,4-二羟基四氢呋喃-2-基]磷酸二氢甲酯 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 甲醇 、 乙二醇甲醚 、 水 、 溶剂黄146 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 12.0h， 生成 monosodium mono(((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((6-(6-(2-iodoacetamido)hexanamido)hexyl)amino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl triphosphate)
  参考文献：
  名称：

  Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups

  摘要：

  Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

  DOI：

  10.1021/jm00346a009
• 作为产物：
  描述：

  1,6-己二胺 、 6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐 以 水 为溶剂， 反应 6.0h， 生成 [(2R,3S,4R,5R)-5-[6-(6-氨基己基氨基)嘌呤-9-基]-3,4-二羟基四氢呋喃-2-基]磷酸二氢甲酯
  参考文献：
  名称：

  Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups

  摘要：

  Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

  DOI：

  10.1021/jm00346a009

文献信息

• Cellular delivery of dinucleotides by conjugation with small molecules: targeting translation initiation for anticancer applications
  作者：Natalia Kleczewska、Pawel J. Sikorski、Zofia Warminska、Lukasz Markiewicz、Renata Kasprzyk、Natalia Baran、Karina Kwapiszewska、Aneta Karpinska、Jaroslaw Michalski、Robert Holyst、Joanna Kowalska、Jacek Jemielity

  DOI：10.1039/d1sc02143e

  日期：——

  molecule ligands – folic acid, biotin, glucose, and cholesterol – to deliver both hydrolyzable and cleavage-resistant cap analogs into cells. A broad structure–activity relationship (SAR) study using model fluorescent probes and cap–ligand conjugates showed that cholesterol greatly facilitates uptake of cap analogs without disturbing the interactions with eIF4E. The most potent cholesterol conjugate identified

  靶向帽依赖性翻译起始是可能导致新型抗癌疗法开发的实验方法之一。合成二核苷 5',5'-三磷酸帽类似物是体外真核翻译起始因子 4E (eIF4E) 的有效拮抗剂，可以抵消癌细胞中 eIF4E 水平升高；然而，将这些化合物转化为治疗剂仍然具有挑战性——它们不容易渗透到细胞中，并且容易受到酶促裂解。在这里，我们测试了几种小分子配体（叶酸、生物素、葡萄糖和胆固醇）将可水解和抗裂解帽类似物递送到细胞中的潜力。使用模型荧光探针和帽子-配体缀合物进行的广泛结构-活性关系 (SAR) 研究表明，胆固醇极大地促进帽子类似物的摄取，而不干扰与 eIF4E 的相互作用。鉴定出的最有效的胆固醇缀合物对癌细胞表现出凋亡介导的细胞毒性。
• RNA CONTAINING COENZYMES, BIOTIN, OR FLUOROPHORES, AND METHODS FOR THEIR PREPARATION AND USE
  申请人：UNIVERSITY OF SOUTHERN MISSISSIPPI

  公开号：US20040241649A1

  公开（公告）日：2004-12-02

  Materials and methods for incorporating adenosine derivatives into the 5′ end of transcribed RNA are disclosed. Adenosine derivatives include naturally occurring compounds such as Coenzyme A, NAD, and FAD, as well as various non-naturally occurring compounds. The derivatives can be used to impart desirable properties to the RNA such as fluorescence, the ability to bind to receptors or ligands, and improved catalytic activity. The transcribed RNAs can be used in a variety of applications including nucleic acid detection, designed or random generation of catalytic RNAs, antisense applications, and in the study of RNA structure and function

  公开了将腺苷衍生物并入转录RNA 5'端的材料和方法。腺苷衍生物包括天然化合物，如辅酶A，NAD和FAD，以及各种非自然发生的化合物。这些衍生物可用于赋予RNA所需的性质，如荧光，与受体或配体结合的能力以及改善催化活性。转录的RNA可用于各种应用，包括核酸检测，设计或随机生成催化RNA，反义应用以及用于研究RNA结构和功能。
• Melanocortin-4 receptor binding compounds and methods of use thereof
  申请人：Vos Tricia J.

  公开号：US20080269217A1

  公开（公告）日：2008-10-30

  Provided are MC4-R binding compounds of the formula XVII: wherein L 2 is a linker group, and P 1 , P 2 , P 3 , P 4 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , t, s, and R are as described in the specification. Methods of using the compounds to treat MC4-R associated disorders, such as disorders associated with weight loss, are also provided.

  提供的是公式XVII的MC4-R结合化合物： 其中L2是连接基团，而P1，P2，P3，P4，Z1，Z2，Z3，Z4，Z5，t，s和R如规范所述。还提供了使用这些化合物治疗MC4-R相关疾病的方法，例如与体重减轻相关的疾病。
• Assay method for group transfer reactions
  申请人：Lowery Robert

  公开号：US20060172335A1

  公开（公告）日：2006-08-03

  The present invention relates to methods for detecting, quantifying and high throughput screening of donor-products and the catalytic activities generating the donor-products in group-transfer reactions catalyzed by adenosine triphosphatase (ATPase) or guanine triphosphatase (GTPase). The invention further provides immunoassays, antibodies and kits that may be used to practice the methods of the invention.

  本发明涉及在由腺苷三磷酸酶（ATPase）或鸟嘌呤三磷酸酶（GTPase）催化的基团转移反应中检测、定量和高通量筛选供体-产物及生成供体-产物的催化活性的方法。本发明进一步提供了可用于实施本发明方法的免疫测定、抗体和试剂盒。
• Multifunctional dinucleotide analogs for the generation of complex RNA conjugates
  作者：Felix Hausch、Andres Jäschke

  DOI：10.1016/s0040-4020(00)01114-5

  日期：2001.2

  Oligonucleotide conjugates are needed for in vitro selection schemes aiming at reactions between small, organic reactants. A general strategy is provided for the generation of the required RNA reactant conjugates based on multifunctional dinucleotide analogs. These modified dinucleotides allow for enzymatic ligation to native or enzymatically transcribed RNAs. They further contain a flexible polyethylene glycol spacer for correct spatial positioning and a photolabile cleavage site for selective release. The dinucleotides can be derivatized with the desired organic compounds by activated ester chemistry as was demonstrated by coupling to several nucleobases and nucleotides. (C) 2001 Elsevier Science Ltd. All rights reserved.