6-氨基-9-[3,4-二羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]四氢呋喃-2-基]-嘌呤 | 485-84-7

• 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: 6-氨基-9-[3,4-二羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]四氢呋喃-2-基]-嘌呤
• 中文别名: 二环[3.1.0]己烷-6-羧酸,2-(羧基氨基)-,(1R,5S,6R)-rel-[局部的]-(9CI)
• 英文名称: adenosine 5'-phosphosulfate
• 英文别名: Adenosine-5'-phosphosulfate；adenosine 3′-phosphate 5′-phosphosulfate；Adenosine 5′-phosphosulfate；adenosine 5'-phosphosulphate；adenosine phosphosulfate；APS；[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl sulfo hydrogen phosphate
• CAS: 485-84-7
• 化学式: C₁₀H₁₄N₅O₁₀PS
• 分子量: 427.288
• InChiKey: IRLPACMLTUPBCL-KQYNXXCUSA-N

物化性质

• 物理描述：
  Solid
• 碰撞截面：
  190.4 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)：
  -3.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  238
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  6-氨基-9-[3,4-二羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]四氢呋喃-2-基]-嘌呤 在 Arabidopsis thaliana Hint₄ 作用下， 生成 二磷酸腺苷
  参考文献：
  名称：

  Dual activity of certain HIT-proteins:A. thalianaHint4 andC. elegansDcpS act on adenosine 5′-phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP)

  摘要：

  Histidine triad (HIT)‐family proteins interact with different mono‐ and dinucleotides and catalyze their hydrolysis. During a study of the substrate specificity of seven HIT‐family proteins, we have shown that each can act as a sulfohydrolase, catalyzing the liberation of AMP from adenosine 5′‐phosphosulfate (APS or SO4‐pA). However, in the presence of orthophosphate, Arabidopsis thaliana Hint4 and Caenorhabditis elegans DcpS also behaved as APS phosphorylases, forming ADP. Low pH promoted the phosphorolytic and high pH the hydrolytic activities. These proteins, and in particular Hint4, also catalyzed hydrolysis or phosphorolysis of some other adenylyl‐derivatives but at lower rates than those for APS cleavage. A mechanism for these activities is proposed and the possible role of some HIT‐proteins in APS metabolism is discussed.

  DOI：

  10.1016/j.febslet.2009.11.003
• 作为产物：
  描述：

  5'-腺嘌呤核苷酸 在 吡啶 、 硫酸 、 N,N'-二环己基碳二亚胺 作用下， 生成 6-氨基-9-[3,4-二羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]四氢呋喃-2-基]-嘌呤
  参考文献：
  名称：

  Chemical Synthesis of Adenosine 5'-Phosphosulfates¹

  摘要：

  DOI：

  10.1021/ja01513a032
• 作为试剂：
  描述：

  nitrobenzyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside 在 palladium on activated charcoal 四甲基乙二胺 、 galactosyl transferase 、 HEPES buffer 、 氢气 、 sodium methylate 、 ammonium formate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 丙烯酰胺 、 6-氨基-9-[3,4-二羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]四氢呋喃-2-基]-嘌呤 、 α-lactalbumin 作用下， 以 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 109.08h， 生成 N-acetyl-D-lactosamine
  参考文献：
  名称：

  High performance polymer supports for enzyme-assisted synthesis of glycoconjugates

  摘要：

  Efficient and practical methodology for the construction of carbohydrates, including oligosaccharide derivatives and sphingoglycolipids, was established on the basis of a water-soluble polymer supports having unique linkers that can be cleaved by specific conditions. Novel glycomonomers for the construction of polymer supports were synthesized and copolymerized with acrylamide to give three types of water-soluble glycopolymers having primer sugars through the specific linkers containing (i) p-substituted benzyl group, (ii) L-phenylalanine residue, and (iii) ceramide-mimetic L-serine derivative, respectively. These glycopolymers were employed for sugar elongation reactions with glycosyl transferases such as GlcNAc beta 1,4-galactosyl transferase, beta Gal1-->3/4GlcNAc alpha-2,6-sialyl transferase, and beta Gal1-->3/4GlcNAc alpha-2,3-sialyl transferase in the presence of each sugar nucleotide as glycosyl donor to afford polymers having N-acetyllactosamine, sialyl alpha-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-->3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis with alpha-chymotrypsin, or transglycosylation to ceramide with ceramide glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha-(2-->6) N-acetyllactosamine derivative having a terminal amino group, and ganglioside GM3 in high yield. (C) 1998 Elsevier Science Ltd.

  DOI：

  10.1016/s0008-6215(97)10051-9

文献信息

• [EN] SUBSTITUTED PYRIDONES AS INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASE (PARP)<br/>[FR] PYRIDONES SUBSTITUES INHIBITEURS DE LA POLY(ADP-RIBOSE) POLYMERASE (PARP)
  申请人：AVENTIS PHARMA INC

  公开号：WO2005097750A1

  公开（公告）日：2005-10-20

  The present invention discloses and claims a series of 2,3,5-substituted pyridone derivatives as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5'-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.

  本发明公开并声明了一系列如下定义的2,3,5-取代吡啶酮衍生物。本发明还涉及制备这些化合物的方法。本发明的化合物是多聚腺苷酸二磷酸核糖酶（PARP）的抑制剂，因此在制药剂中特别用于治疗和/或预防各种疾病，包括与中枢神经系统和心血管疾病相关的疾病。
• [EN] NOVEL SYNTHETIC DINUCLEOSIDE POLYPHOSPHATE ANALOGS AND THEIR USE AS NEW THERAPEUTIC AND/OR DIAGNOSTIC MODALITIES<br/>[FR] NOUVEAUX ANALOGUES SYNTHÉTIQUES DE DINUCLÉOSIDE POLYPHOSPHATE ET LEUR UTILISATION COMME NOUVELLES MODALITÉS THÉRAPEUTIQUES ET/OU DIAGNOSTIQUES
  申请人：ZATA PHARMACEUTICALS INC

  公开号：WO2010056795A1

  公开（公告）日：2010-05-20

  The invention provides novel synthetic dinucleoside polyphosphate analogs and their use as therapeutic compounds and/or diagnostic tools for the treatment and diagnosis of various human diseases and metabolic disorders.

  这项发明提供了新型合成二核苷酸聚磷酸盐类似物及其作为治疗化合物和/或诊断工具用于治疗和诊断各种人类疾病和代谢紊乱。
• [EN] 5'-PHOSPHOROTHIOLATE MRNA 5'-END (CAP) ANALOGS, MRNA COMPRISING THE SAME, METHOD OF OBTAINING AND USES THEREOF<br/>[FR] ANALOGUES D'EXTRÉMITÉ 5' (COIFFE) D'ARNM 5'-PHOSPHOROTHIOLATE , ARNM LES COMPRENANT, LEUR PROCÉDÉ D'OBTENTION ET UTILISATIONS
  申请人：UNIV WARSZAWSKI

  公开号：WO2017130151A1

  公开（公告）日：2017-08-03

  The present invention relates to nucleotides, analogs of mRNA 5'-end (cap) containing sulfur atom at the position 5' of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, wh ich modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5' end with mRNA 5'-end (cap) analogs containing 5'- phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L1 and L2 are independently selected from the group comprising O and S, wherein at least one of L1 and L2 is not O.

  本发明涉及核苷酸，含有硫原子的mRNA 5'-端（帽子）的类似物，在7-甲基鸟苷核苷酸的5'位置。所公开的化合物被DcpS酶（去帽清道夫）识别（结合并不水解），因此可能作为其抑制剂在治疗中发挥作用。DcpS是帽子特异性酶，具有焦磷酸酶活性，已被确定为治疗脊髓性肌萎缩（SMA）的治疗靶点。所公开的一些化合物在磷酸链中具有额外的修饰，调节它们对DcpS酶的亲和力。本发明还涉及在mRNA的5'端修饰了含有5'-磷硫酸酯基团的mRNA 5'-端（帽子）类似物的mRNAs，这些mRNAs在细胞条件下具有增强的稳定性和翻译活性，以及它们的制备方法，用途和含有它们的制药配方，其中L1和L2分别选择自包括O和S的组中，其中至少一个L1和L2不是O。
• [EN] THROMBIN INHIBITORS FOR TREATMENT OF STROKE AND RELATED COAGULATIVE DISORDERS<br/>[FR] INHIBITEURS DE THROMBINE POUR LE TRAITEMENT D'UN ACCIDENT VASCULAIRE CÉRÉBRAL ET DE TROUBLES DE COAGULATION ASSOCIÉS
  申请人：UNIV SYDNEY

  公开号：WO2018107247A1

  公开（公告）日：2018-06-21

  The invention relates to the treatment of stroke and related diseases, to fibrin clot formation and related thrombin activity, and to preparation of compounds, in particular, peptides and polypeptides for inhibiting, or for modifying the cleavage of fibrinogen by thrombin.

  该发明涉及中风及相关疾病的治疗，涉及纤维蛋白凝块形成和相关的凝血酶活性，以及制备化合物，特别是用于抑制或修改凝血酶对纤维蛋白原的切割的肽和多肽。
• Recognition of different nucleotidyl-derivatives as substrates of reactions catalyzed by various HIT-proteins
  作者：Andrzej Guranowski、Anna Maria Wojdyła、Jarosław Zimny、Anna Wypijewska、Joanna Kowalska、Maciej Łukaszewicz、Jacek Jemielity、Edward Darżynkiewicz、Agata Jagiełło、Paweł Bieganowski

  DOI：10.1039/b9nj00660e

  日期：——

  Proteins that have a histidine triad in their active sites belong to the HIT-protein superfamily. They are ubiquitous, are involved in the metabolism of different nucleotides and catalyze their hydrolysis and/or phosphorolysis liberating either the corresponding 5′-NMP or 5′-NDP, respectively. We studied substrate specificity of nine recombinant HIT-proteins with adenosine 5′-phosphosulfate (1), adenosine 5′-phosphoramidate (2), adenosine 5′-phosphorothioate (3), adenosine 5′-phosphorofluoride (4), diadenosine 5′,5′′′-P1,P3-triphosphate (5), di(7-methylguanosine) 5′,5′′′-P1,P3-triphosphate (6) and adenosine 5′-hypophosphate (7). Preferences for the recognition of these compounds as substrates by individual proteins differed. All the proteins hydrolyzed (1) but the Arabidopsis thaliana Hint1 did it very slowly. None of the proteins cleaved (7). Only A. thaliana Hint1 and Escherichia coli HinT hydrolyzed (3). Three proteins known as dinucleoside triphosphatases, human and A. thaliana Fhit-proteins and Trypanosoma brucei HIT-45, cleaved (1), (2), (4), (5) and (6). Caenorhabditis elegans decapping protein DcpS degraded (1), (5), (6) and poorly (4). A. thaliana aprataxin-like protein and Hint4 hydrolyzed only (1), (2) and (4), in that order of efficiency. Velocities of those reactions and some Km values were determined. Applicability of this study to the metabolism of certain nucleotidyl-derivatives is discussed.

  活性位点具有组氨酸三联体的蛋白质属于 HIT 蛋白质超家族。它们无处不在，参与不同核苷酸的代谢并催化它们的水解和/或磷酸解，分别释放相应的 5'-NMP 或 5'-NDP。我们研究了九种重组 HIT 蛋白的底物特异性，其中包括腺苷 5'-磷酸硫酸酯 (1)、腺苷 5'-氨基磷酸酯 (2)、腺苷 5'-硫代磷酸酯 (3)、腺苷 5'-氟化磷 (4)、二腺苷 5' ,5'''-P1,P3-三磷酸 (5)、二(7-甲基鸟苷) 5',5'''-P1,P3-三磷酸 (6) 和腺苷 5'-连二磷酸 (7)。各个蛋白质对这些化合物作为底物的识别偏好不同。所有蛋白质都会水解 (1)，但拟南芥 Hint1 的水解速度非常缓慢。没有蛋白质被裂解 (7)。仅拟南芥 Hint1 和大肠杆菌 HinT 会水解 (3)。被称为二核苷三磷酸酶、人类和拟南芥 Fhit 蛋白以及布氏锥虫 HIT-45 的三种蛋白质被切割 (1)、(2)、(4)、(5) 和 (6)。秀丽隐杆线虫脱帽蛋白 DcpS 降解 (1)、(5)、(6) 和较差 (4)。拟南芥 aprataxin 样蛋白和 Hint4 按效率顺序仅水解 (1)、(2) 和 (4)。确定了这些反应的速度和一些 Km 值。讨论了本研究对某些核苷酸衍生物代谢的适用性。