((2R,3R,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-(4-azidobutoxy)-3-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl sulfamate | 1548502-93-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: ((2R,3R,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-(4-azidobutoxy)-3-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl sulfamate
• CAS: 1548502-93-7
• 化学式: C₂₀H₃₅N₉O₆SSi
• 分子量: 557.706
• InChiKey: AHIYMYYQWGBWTL-NVQRDWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  37.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  215.46
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  ((2R,3R,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-(4-azidobutoxy)-3-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl sulfamate 在 caesium carbonate 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

  摘要：

  The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A-domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors.

  DOI：

  10.3762/bjoc.20.39
• 作为产物：
  描述：

  腺苷 在 咪唑 、 4-二甲氨基吡啶 、 氨基磺酰氯 、 四丁基碘化铵 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 ((2R,3R,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-(4-azidobutoxy)-3-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl sulfamate
  参考文献：
  名称：

  Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

  摘要：

  The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A-domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors.

  DOI：

  10.3762/bjoc.20.39

文献信息

• Active site-directed proteomic probes for adenylation domains in nonribosomal peptide synthetases
  作者：Sho Konno、Fumihiro Ishikawa、Takehiro Suzuki、Naoshi Dohmae、Michael D. Burkart、Hideaki Kakeya

  DOI：10.1039/c4cc09412c

  日期：——

  Active site-directed proteomic probes coupled to the 5′-O-N-(aminoacyl)sulfamoyladenosine (AMS) scaffold with a clickable benzophenone functionality selectively target nonribosomal peptide synthetase (NRPS) adenylation (A) domains in natural product producer proteomes by ligand-directed protein labeling.

  将主动定向蛋白质组学探针与可点击的苯酮功能基团偶联到5'-O-N-(氨酰基)磺胺腺苷（AMS）支架上，通过配体定向蛋白质标记选择性地靶向天然产物生产者蛋白质组中的非核糖体肽合酶（NRPS）腺苷化（A）结构域。
• Specific enrichment of nonribosomal peptide synthetase module by an affinity probe for adenylation domains
  作者：Fumihiro Ishikawa、Hideaki Kakeya

  DOI：10.1016/j.bmcl.2013.12.082

  日期：2014.2

  (NRPS)-polyketide synthase (PKS) hybrids and NRPSs. A 5′-O-sulfamoyladenosine (AMS) non-hydrolyzable analogue of adenosine monophosphate (AMP) has been reported as a scaffold for the design of inhibitors exhibiting tight binding of adenylation enzymes. Here we describe the application of an affinity probe for A domains. Our synthetic probe, a biotinylated l-Phe-AMS (l-Phe-AMS-biotin) specifically targets the

  我们针对腺苷酸化（A）域的亲和力探针的开发目标，该亲和力探针可促进非核糖体肽合成酶（NRPS）-聚酮化合物合酶（PKS）杂种和NRPSs中含有A域的模块的富集，鉴定和定量。已经报道了单磷酸腺苷（AMP）的5'- O-氨磺酰腺苷（AMS）不可水解类似物作为支架的支架，用于设计表现出腺苷酸化酶紧密结合的抑制剂。在这里，我们描述了针对A域的亲和探针的应用。我们的合成探针，一种生物素化的I -Phe-AMS（I -Phe-AMS-生物素）专门针对NRPS模块中的A结构域，从而激活I -Phe-AMS。-在重组NRPS酶系统和整个蛋白质组中均转化为氨基酰基腺苷酸中间体。