Guanosine 5'-triphosphate | 86-01-1

• 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 - 嘌呤核苷酸
• 英文名称: Guanosine 5'-triphosphate
• 英文别名: dGTP；GTP；guanosine triphosphate；guanosine 5′-triphosphate；Guanosine 5'-(tetrahydrogen triphosphate)；guanosine-5’-triphosphate；Guanosine Triphosphate；[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 86-01-1
• 化学式: C₁₀H₁₆N₅O₁₄P₃
• 分子量: 523.183
• InChiKey: XKMLYUALXHKNFT-UUOKFMHZSA-N

物化性质

• 密度：
  2.75±0.1 g/cm3(Predicted)
• 溶解度：
  Soluble (water)
• 物理描述：
  Solid
• 碰撞截面：
  196 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]
• 稳定性/保质期：
  该产品为白色或类白色的粉末状物质，无特殊气味，吸湿性强。它容易溶解于水，但在醇和氯仿中不易溶解。

计算性质

• 辛醇/水分配系数(LogP)：
  -5.7
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  295
• 氢给体数：
  8
• 氢受体数：
  16

安全信息

• 储存条件：
  2-8°C

制备方法与用途

化学性质
本品为白色或类白色粉末，无臭味，并具有吸湿性。它在水中易溶，在醇和氯仿中不溶解。

用途
用于辅助治疗慢性肝炎、进行性肌萎缩以及视力减退等疾病。

生产方法
采用GMP作为原料，通过发酵法制造。具体步骤如下：

1. 将酵母保温于28-30℃，使用氢氧化钠调整pH值至7，发酵4小时后，酵母开始沉淀，过滤除去酵母，得到酶液。
2. 将GMP溶解成8%-10%的水溶液，并加入9倍体积的酶液，在同样条件下继续发酵约3小时，直至反应终点。随后进行过滤，滤液通过含有2%硅藻土的搅拌过滤。
3. 滤液加水稀释至GTP浓度为0.3%，并通过强碱性季铵I型阴离子交换树脂柱（717）吸附。

洗脱与再次吸附
树脂吸附物使用0.04-0.07mol/L氯化钠溶液和0.04-0.07mol/L盐酸进行洗脱。随后，再用717树脂进一步吸附。

最终处理
二次树脂吸附物首先使用0.04-0.07mol/L的氯化钠和0.01mol/L的盐酸洗脱，然后以0.5-1mol/L的氯化钠溶液进行洗脱。接着加入少量活性炭和硅藻土搅拌40分钟，过滤后，将滤液与3倍体积的乙醇混合静置，过滤，并用无水乙醇及无水乙醚洗涤滤饼。最后，在真空条件下干燥，获得三磷酸鸟苷钠成品。

吸附物[氯化钠]→洗脱液[活性炭，硅藻土]→[40分钟]洗脱液[乙醇]→GTP[无水乙醇，无水乙醚]→GTP-Na。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  鸟苷(5')四磷酰(5')鸟苷	Diguanosine 5'-tetraphosphate	4130-19-2	C20H28N10O21P4	868.392
  鸟苷-5’-二磷酸	guanosine-5'-diphosphate	146-91-8	C10H15N5O11P2	443.204
  鸟苷酸	5'-guanosine monophosphate	85-32-5	C10H14N5O8P	363.224
  鸟苷	GUANOSINE	118-00-3	C10H13N5O5	283.244
  二磷酸腺苷	adenosine 5'-diphosphate	58-64-0	C10H15N5O10P2	427.204
  ——	P(3)-1-(2-Nitro)phenylethylguanosine 5'-O-triphosphate	124830-99-5	C18H23N6O16P3	672.332

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  鸟苷-5’-二磷酸	guanosine-5'-diphosphate	146-91-8	C10H15N5O11P2	443.204
  鸟苷酸	5'-guanosine monophosphate	85-32-5	C10H14N5O8P	363.224
  ——	cyclic guanosine 3',5'-monophosphate	——	C10H12N5O7P	345.208
  ——	8-oxo-rGTP	21238-36-8	C10H16N5O15P3	539.183
  ——	GDP-Fuc	——	C16H25N5O15P2	589.347
  [(2R,3S,4R,5R)-5-(2-氨基-6-氧代-3,6-二氢-9H-嘌呤-9-基)-3,4-二羟基四氢-2-呋喃基]甲基(2R,3S,4S,5S,6R)-3,4,5-三羟基-6-甲基四氢-2H-吡喃-2-基二氢二磷酸酯	GDP-D-Rha	15839-74-4	C16H25N5O15P2	589.347
  ——	guanosine 5'-diphospho-D-mannose	——	C16H25N5O16P2	605.346
  [5-(2-氨基-6-氧代-3,6-二氢-9H-嘌呤-9-基)-3,4-二羟基四氢-2-呋喃基]甲基 3,4,5-三羟基-6-(羟基甲基)四氢-2H-吡喃-2-基二氢二磷酸酯	GDP-L-galactose	6815-91-4	C16H25N5O16P2	605.346
  鸟苷	GUANOSINE	118-00-3	C10H13N5O5	283.244
  ——	Gp(2'-5')G	——	C20H25N10O12P	628.452

反应信息

• 作为反应物：
  描述：

  Guanosine 5'-triphosphate 在 磷酸单硝基苯基酯 、 D-山梨糖 、 乙醇胺盐酸盐 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 0.08h， 生成 鸟苷
  参考文献：
  名称：

  Characteristics of Psychrophilic Alkaline Phosphatase

  摘要：

  一种嗜冷菌（希瓦氏菌属）的磷酸酶通过硫酸铵分级分离，随后进行连续的柱层析纯化。纯化后的酶在天然聚丙烯酰胺凝胶电泳和SDS-聚丙烯酰胺凝胶电泳中呈现电泳均一性。根据其氨基酸组成，其分子量为41,826。该酶的最适活性pH值为9.8，对去磷酸化的底物如ATP、焦磷酸盐、甘油磷酸盐等具有广泛的底物特异性。金属离子如Mg²⁺、Mn²⁺和Co²⁺可以增强其活性。最大活性在40°C时被观察到，而在0°C时该酶显示出40°C活性的39%。然而，该酶在20°C和pH 9.8时倾向于失去活性。这些结果表明，纯化后的酶是一种碱性磷酸酶，具有在低温下高催化效率和中温下逐渐失活的特性。

  DOI：

  10.1271/bbb.62.2246
• 作为产物：
  描述：

  鸟苷酸 在 盐酸 、 乙二胺四乙酸 、 piruvate kinase 、 T₅ bacteriophage deoxynucleoside monophosphate kinase 、 potassium chloride 、 5’-三磷酸腺苷 、 还原型辅酶Ⅰ 、 magnesium chloride 、 L-lactate dehydrogenase 作用下， 生成 Guanosine 5'-triphosphate
  参考文献：
  名称：

  T5噬菌体脱氧核糖核苷单磷酸激酶的底物特异性及其在[α-32P]d/rNTP合成中的应用

  摘要：

  噬菌体 T5 脱氧核苷单磷酸激酶（dNMP 激酶，EC 2.7.4.13）显示可催化 d2CMP 和核糖核苷酸 AMP、GMP 和 CMP 的磷酸化，但不磷酸化 UMP。对于磷酰基的天然受体，发现了 km 和 kcat。T5 dNMP 激酶作为能够磷酸化标记的 r/dNMP 的通用酶的适用性已被证明可用于合成 [α-32P]rNTP 和 [α-32P]dNTP。

  DOI：

  10.1134/s1068162009060090
• 作为试剂：
  描述：

  2-氧代丁二酸 在 pyruvate kinase 、 recombinant rat cytosolic phosphoenolpyruvate carboxykinase 、 二磷酸腺苷 、 Guanosine 5'-triphosphate 、 还原型辅酶Ⅰ 、 magnesium chloride 、 manganese(ll) chloride 、 L-lactate dehydrogenase 、 1,4-二巯基-2,3-丁二醇 作用下， 以 水 为溶剂， 生成 phosphoenolpyruvate
  参考文献：
  名称：

  Increasing the Conformational Entropy of the Ω-Loop Lid Domain in Phosphoenolpyruvate Carboxykinase Impairs Catalysis and Decreases Catalytic Fidelity,

  摘要：

  Many studies have shown that the dynamic motions of individual protein segments can play an important role in enzyme function. Recent structural studies of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) demonstrate that PEPCK contains a 10-residue Omega-loop domain that acts as an active site lid. On the basis of these structural studies, we have previously proposed a model for the mechanism of PEPCK catalysis in which the conformation of this mobile lid domain is energetically coupled to ligand binding, resulting in the closed conformation of the lid, necessary for correct substrate positioning, becoming more energetically favorable as ligands associate with the enzyme. Here we test this model by introducing a point mutation (A467G) into the center of the Omega-loop lid that is designed to increase the entropic penalty for lid closure. Structural and kinetic characterization of this mutant enzyme demonstrates that the mutation has decreased the favorability of the enzyme adapting the closed lid conformation. As a consequence of this shift in the equilibrium defining the conformation of the active site lid, the enzyme's ability to stabilize the reaction intermediate is weakened, resulting in catalytic defect. This stabilization is initially surprising, as the lid domain makes no direct contacts with the etiolate intermediate formed during the reaction. Furthermore, during the conversion of OAA to PEP, the destabilization of the lid-closed conformation results in the reaction becoming decoupled as the etiolate intermediate is protonated rather than phosphorylated, resulting in the formation of pyruvate. Taken together, the structural and kinetic characterization of A467G-PEPCK supports our model of the role of the active site lid in catalytic function and demonstrates that the shift in the lowest-energy conformation between open and closed lid states is a function of the free energy available to the enzyme through ligand binding and the entropic penalty for ordering of the 10-residue Omega-loop lid domain.

  DOI：

  10.1021/bi100399e

文献信息

• 5-arylpyrimidines as anticancer agents
  申请人：Zhang Nan

  公开号：US20050075357A1

  公开（公告）日：2005-04-07

  This invention relates to certain 5-arylpyrimidine compounds or a pharmaceutically acceptable salt thereof, and compositions containing said compounds or a pharmaceutically acceptable salt thereof, wherein said compounds are anti-cancer agents useful for the treatment of cancer in mammals. This invention further relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal and further provides a method for the treatment or prevention of cancerous tumors that express multiple drug resistance (MDR) or are resistant because of MDR, in a mammal in need thereof which method comprises administering to said mammal an effective amount of said compounds or a pharmaceutically acceptable salt thereof. More specifically, the present invention relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof by promotion of microtubule polymerization which comprises administering to said mammal an effective amount of said compounds and pharmaceutically acceptable salts thereof.

  这项发明涉及某些5-芳基嘧啶化合物或其药用盐，以及含有所述化合物或其药用盐的组合物，其中所述化合物是抗癌剂，可用于治疗哺乳动物的癌症。该发明还涉及一种治疗或抑制哺乳动物体内癌细胞和相关疾病生长的方法，并进一步提供了一种治疗或预防表达多药耐药性（MDR）或因MDR耐药的癌症肿瘤的方法，该方法包括向所述哺乳动物体内施用所述化合物或其药用盐的有效量。更具体地，本发明涉及通过促进微管聚合来治疗或抑制哺乳动物体内癌细胞和相关疾病的方法，该方法包括向所述哺乳动物体内施用所述化合物及其药用盐的有效量。
• [EN] ELECTROCHEMICALLY-CLEAVABLE LINKERS<br/>[FR] LIEURS CLIVABLES PAR VOIE ÉLECTROCHIMIQUE
  申请人：MICROSOFT TECHNOLOGY LICENSING LLC

  公开号：WO2021158412A1

  公开（公告）日：2021-08-12

  This disclosure provides electrochemically-cleavable linkers with cleavage potentials that are less than the redox potential of the solvent in which the linkers are used. In some applications, the solvent may be water or an aqueous buffer solution. The linkers may be used to link a nucleotide to a bound group. The linkers include a cleavable group which may be one of a methoxybenzyl alcohol, an ester, a propargyl thioether, or a trichloroethyl ether. The linkers may be cleaved in solvent by generating an electrode potential that is less than the redox potential of the solvent. In some implementations, an electrode array may be used to generate localized electrode potentials which selectively cleave linkers bound to the activated electrode. Uses for the linkers include attachment of blocking groups to nucleotides in enzymatic oligonucleotide synthesis.

  这份披露提供了具有低于使用的溶剂的氧化还原电位的可电化学裂解连接物。在某些应用中，溶剂可能是水或水溶液缓冲液。这些连接物可用于将核苷酸连接到结合基团。连接物包括可裂解基团，可能是甲氧基苯甲醇、酯、丙炔硫醚或三氯乙基醚中的一种。通过产生低于溶剂的氧化还原电位的电极电位，可以在溶剂中裂解这些连接物。在某些实施中，可以使用电极阵列来产生局部电极电位，从而选择性地裂解与激活电极结合的连接物。这些连接物的用途包括在酶催化寡核苷酸合成中将阻断基团附着到核苷酸上。
• 6-N-Linked Heterocycle-Substituted 2,3,4,5-Tetrahydro-1H-Benzo[d]Azepines as 5-Ht2c Receptor Agonists
  申请人：Briner Karin

  公开号：US20080214520A1

  公开（公告）日：2008-09-04

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT 2C receptor agonists for the treatment of 5-HT 2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: Formula (I) where: R 6 is selected from the group consisting of (a, b, c, d, e) and other substituents are as defined in the specification.

  本发明提供了Formula I的6-取代的2,3,4,5-四氢-1H-苯并[d]氮杂环庚烯作为选择性5-HT2C受体激动剂，用于治疗与5-HT2C相关的疾病，包括肥胖症、强迫症、抑郁症和焦虑症：Formula (I)其中：R6选自(a、b、c、d、e)等基团组成的群，其他取代基如规范中定义。
• POLY(PHOSPHOESTERS) FOR DELIVERY OF NUCLEIC ACIDS
  申请人：TRANSLATE BIO, INC.

  公开号：US20200277446A1

  公开（公告）日：2020-09-03

  Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R 1 , R 2 , L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.

  揭示了包含A基团的聚合物，该基团是化学式I的基团：及其药用可接受的盐，其中R、R1、R2、L、n1和n2如本文所定义。这些聚合物对于将核酸传递给受试者是有用的。这些聚合物和包含这些聚合物和核酸的药用可接受组合物可用于治疗各种疾病、疾病和症状。
• [EN] COMPOSITIONS AND METHODS FOR SYNTHESIS OF PHOSPHORYLATED MOLECULES<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULES PHOSPHORYLÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195494A1

  公开（公告）日：2019-10-10

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.

  这项发明提供了合成磷酸化有机化合物的组合物和方法，包括核苷三磷酸。