Tiazofurin adenosine disulfide | 1186091-86-0

• 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: Tiazofurin adenosine disulfide
• 英文别名: (tiazofurin-5'-yl)(adenosin-5'-yl) disulfide；(Tiazofurin-5''-yl)(adenosin-5''-yl)disulfide；2-[(2R,3R,4S,5S)-5-[[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyldisulfanyl]methyl]-3,4-dihydroxyoxolan-2-yl]-1,3-thiazole-4-carboxamide
• CAS: 1186091-86-0
• 化学式: C₁₉H₂₃N₇O₇S₃
• 分子量: 557.632
• InChiKey: JIHGLORHRJMYSK-QZTLEVGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  304
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  2-((2R,3R,4S,5S)-3,4-dihydroxy-5-(mercaptomethyl)tetrahydrofuran-2-yl)thiazole-4-carboxamide 、 5'-硫代腺苷 在 碘 作用下， 以 甲醇 、 乙醇 为溶剂， 以28 mg的产率得到Ditiazofurin disulfide
  参考文献：
  名称：

  Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside disulfide mimics of nicotinamide adenine dinucleotide analogues

  摘要：

  Diadenosine disulfide (5) was reported to inhibit NAD kinase from Lysteria monocytogenes and the crystal structure of the enzyme-inhibitor complex has been solved. We have synthesized tiazofurin adenosine disulfide (4) and the disulfide 5, and found that these compounds were moderate inhibitors of human NAD kinase (IC50 = 110 mu M and IC50 = 87 mu M, respectively) and Mycobacterium tuberculosis NAD kinase (IC50 = 80 mu M and IC50 = 45 mu M, respectively). We also found that NAD mimics with a short disulfide (-S-S-) moiety were able to bind in the folded (compact) conformation but not in the common extended conformation, which requires the presence of a longer pyrophosphate (-O-P-O-P-O-) linkage. Since majority of NAD-dependent enzymes bind NAD in the extended conformation, selective inhibition of NAD kinases by disulfide analogues has been observed. Introduction of bromine at the C8 of the adenine ring restricted the adenosine moiety of diadenosine disulfides to the syn conformation making it even more compact. The 8-bromoadenosine adenosine disulfide (14) and its di(8-bromoadenosine) analogue (15) were found to be the most potent inhibitors of human (IC50 = 6 mu M) and mycobacterium NAD kinase (IC50 = 14-19 mu M reported so far. None of the disulfide analogues showed inhibition of lactate-, and inosine monophosphate-dehydrogenase (IMPDH), enzymes that bind NAD in the extended conformation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.013

文献信息

• Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside disulfide mimics of nicotinamide adenine dinucleotide analogues
  作者：Riccardo Petrelli、Yuk Yin Sham、Liqiang Chen、Krzysztof Felczak、Eric Bennett、Daniel Wilson、Courtney Aldrich、Jose S. Yu、Loredana Cappellacci、Palmarisa Franchetti、Mario Grifantini、Francesca Mazzola、Michele Di Stefano、Giulio Magni、Krzysztof W. Pankiewicz

  DOI：10.1016/j.bmc.2009.06.013

  日期：2009.8

  Diadenosine disulfide (5) was reported to inhibit NAD kinase from Lysteria monocytogenes and the crystal structure of the enzyme-inhibitor complex has been solved. We have synthesized tiazofurin adenosine disulfide (4) and the disulfide 5, and found that these compounds were moderate inhibitors of human NAD kinase (IC50 = 110 mu M and IC50 = 87 mu M, respectively) and Mycobacterium tuberculosis NAD kinase (IC50 = 80 mu M and IC50 = 45 mu M, respectively). We also found that NAD mimics with a short disulfide (-S-S-) moiety were able to bind in the folded (compact) conformation but not in the common extended conformation, which requires the presence of a longer pyrophosphate (-O-P-O-P-O-) linkage. Since majority of NAD-dependent enzymes bind NAD in the extended conformation, selective inhibition of NAD kinases by disulfide analogues has been observed. Introduction of bromine at the C8 of the adenine ring restricted the adenosine moiety of diadenosine disulfides to the syn conformation making it even more compact. The 8-bromoadenosine adenosine disulfide (14) and its di(8-bromoadenosine) analogue (15) were found to be the most potent inhibitors of human (IC50 = 6 mu M) and mycobacterium NAD kinase (IC50 = 14-19 mu M reported so far. None of the disulfide analogues showed inhibition of lactate-, and inosine monophosphate-dehydrogenase (IMPDH), enzymes that bind NAD in the extended conformation. (C) 2009 Elsevier Ltd. All rights reserved.