N⁶-benzyl-S-adenosylhomocysteine | 111109-99-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: N⁶-benzyl-S-adenosylhomocysteine
• 英文别名: S-(N⁶-benzyladenosyl)-L-homocysteine；(S)-2-amino-4-((((2S,3S,4R,5S)-5-(6-(benzylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)thio)butanoic acid；(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid
• CAS: 111109-99-0
• 化学式: C₂₁H₂₆N₆O₅S
• 分子量: 474.541
• InChiKey: LCMRXADLVDEDPG-SWQDORGXSA-N

物化性质

• 沸点：
  811.6±75.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  194
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N⁶-benzyl-S-adenosylhomocysteine 、 碘甲烷 在 甲酸 作用下， 反应 96.0h， 以16.5%的产率得到N6-benzyl-S-adenosylmethionine iodide
  参考文献：
  名称：

  Structure-Guided Design of a Methyl Donor Cofactor That Controls a Viral Histone H3 Lysine 27 Methyltransferase Activity

  摘要：

  vSET (a viral SET domain protein) is an attractive polycomb repressive complex 2 (PRC2) surrogate to study the effect of histone H3 lysine 27 (H3K27) methylation on gene transcription, as both catalyze histone H3K27 trimethylation. To control the enzymatic activity of vSET in vivo with an engineered S-adenosyl-L-methionine (SAM) analogue as methyl donor cofactor, we have carried out structure-guided design, synthesis, and characterization of orthogonal vSET methyltransferase mutant/ SAM analogue pairs using a "bump-and-hole" strategy.

  DOI：

  10.1021/jm201000j
• 作为产物：
  描述：

  6-氯嘌呤核苷 在 六甲基磷酰三胺 、 氯化亚砜 、 potassium iodide 作用下， 以 乙醇 、 水 为溶剂， 生成 N⁶-benzyl-S-adenosylhomocysteine
  参考文献：
  名称：

  等位基因特异性蛋白质甲基转移酶抑制剂的设计

  摘要：

  蛋白质精氨酸甲基转移酶催化甲基从 S-腺苷甲硫氨酸 (SAM) 转移到靶蛋白中的精氨酸侧链，调节转录、RNA 加工和受体介导的信号传导。为了专门解决该家族各个成员的功能作用，我们采用了“凹凸洞”的方法，并设计了一系列针对酵母蛋白的 N(6)-取代的 S-腺苷高半胱氨酸 (SAH) 类似物甲基转移酶 RMT1。在 Rmt1 中发现了一个点突变 (E117G)，这使得该酶容易受到 SAH 类似物的选择性抑制。基于质谱的酶分析表明，N(6)-苄基-和 N(6)-萘甲基-SAH 两种化合物可以抑制突变酶，选择性大于 20。当 E117G 突变被引入酿酒酵母染色体时，Npl3p（一种已知的体内 Rmt1 底物）的甲基化可以通过 N(6)-萘基甲基-SAH 在所得等位基因中适度降低。此外，发现 N(6)-苄基-SAM 类似物可作为正交 SAM 辅因子。相对于选择性大于 67 的野生型酶，这种类似物优先

  DOI：

  10.1021/ja011423j

文献信息

• SELECTIVE INHIBITORS OF HISTONE METHYLTRANSFERASE DOT1L
  申请人：BAYLOR COLLEGE OF MEDICINE

  公开号：US20140100184A1

  公开（公告）日：2014-04-10

  Structure and mechanism based design was used to design potent ribose containing inhibitors of DOT1L with IC 50 values as low as 38 nM. These ribose containing inhibitors exhibit only weak or no activities against four other representative histone lysine and arginine methyltransferases, G9a, SUV39H1, PRMT1 and CARM1.

  利用基于结构和机制的设计方法，设计出了具有IC50值低至38 nM的强效核糖含量的DOT1L抑制剂。这些核糖含量的抑制剂对其他四种代表性组蛋白赖氨酸和精氨酸甲基转移酶，G9a、SUV39H1、PRMT1和CARM1，仅表现出微弱或无活性。
• SAH derived potent and selective EZH2 inhibitors
  作者：Pei-Pei Kung、Buwen Huang、Luke Zehnder、John Tatlock、Patrick Bingham、Cody Krivacic、Ketan Gajiwala、Wade Diehl、Xiu Yu、Karen A. Maegley

  DOI：10.1016/j.bmcl.2015.02.017

  日期：2015.4

  the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50’s against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most

  基于组蛋白甲基转移酶（HMT）抑制剂SAH（S-腺苷-1-同型半胱氨酸）的化学结构，设计了一系列新型的zeste同源物2（EZH2）抑制剂增强剂。这些基于核苷的EZH2抑制剂在同时使用WT PRC2复合物和Y641N突变体PRC2复合物的生化分析中阻止了H3K27处核小体的甲基化。最有效的化合物27对两种复合物分别显示270 nM和70 nM的IC 50值。据我们所知，化合物27是尚未发现的最有效的SAH衍生的EZH2 PRC2复合物的抑制剂。与SAH相比，该化合物还显示出更高的效价，亲脂效率（LipE）和对其他赖氨酸甲基转移酶的选择性。
• Compounds and methods for increasing the immune response to papillomavirus
  申请人：Universitätsklinikum Heidelberg

  公开号：EP2952182A1

  公开（公告）日：2015-12-09

  The present invention relates to a DNA demethylating agent and to a pharmaceutical composition comprising said DNA demethylating agent and at least a pharmaceutical carrier for use in increasing the immune response to papillomavirus (PV) of a subject infected with PV. Further, the present invention relates to the use of a DNA demethylating agent for increasing the immune response to PV of a subject infected with PV. The present invention also relates to a method for increasing the immune response to a PV of a subject infected with said PV, comprising contacting PV-infected cells of said subject infected with PV with a DNA demethylating agent, and, thereby, increasing the immune response to PV of said subject infected with PV. Moreover, the present invention relates to a method of killing a PV-infected cell, comprising contacting said PV-infected cell with a DNA demethylating agent, contacting said PV-infected cell with at least one PV antigen specific T-cell, and, thereby, killing said PV-infected cell.

  本发明涉及一种DNA去甲基化剂和一种药物组合物，该药物组合物包含所述DNA去甲基化剂和至少一种药物载体，用于增加感染乳头瘤病毒（PV）的受试者对乳头瘤病毒（PV）的免疫反应。此外，本发明还涉及 DNA 去甲基化剂用于提高感染 PV 的受试者对 PV 的免疫应答的用途。本发明还涉及一种提高感染了 PV 的受试者对 PV 的免疫应答的方法，包括将感染了 PV 的受试者的 PV 感染细胞与 DNA 去甲基化剂接触，从而提高感染了 PV 的受试者对 PV 的免疫应答。此外，本发明还涉及一种杀死受 PV 感染细胞的方法，包括用 DNA 去甲基化剂接触所述受 PV 感染的细胞，用至少一种 PV 抗原特异性 T 细胞接触所述受 PV 感染的细胞，从而杀死所述受 PV 感染的细胞。
• [EN] COMPOUNDS AND METHODS FOR INCREASING THE IMMUNE RESPONSE TO PAPILLOMAVIRUS<br/>[FR] COMPOSES ET PROCEDES POUR ACCROITRE LA REPONSE IMMUNITAIRE AU VIRUS DU PAPILLOME
  申请人：UNIVERSITÄTSKLINIKUM HEIDELBERG

  公开号：WO2015185611A1

  公开（公告）日：2015-12-10

  The present invention relates to a DNA demethylating agent and to a pharmaceutical composition comprising said DNA demethylating agent and at least a pharmaceutical carrier for use in increasing the immune response to papillomavirus (PV) of a subject infected with PV. Further, the present invention relates to the use of a DNA demethylating agent for increasing the immune response to PV of a subject infected with PV. The present invention also relates to a method for increasing the immune response to a PV of a subject infected with said PV, comprising contacting PV-infected cells of said subject infected with PV with a DNA demethylating agent, and, thereby, increasing the immune response to PV of said subject infected with PV. Moreover, the present invention relates to a method of killing a PV-infected cell, comprising contacting said PV-infected cell with a DNA demethylating agent, contacting said PV-infected cell with at least one PV antigen specific T-cell, and, thereby, killing said PV-infected cell.