neomycin thioisocyanate | 439697-28-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: neomycin thioisocyanate
• 英文别名: tert-butyl N-[(1S,2R,3R,4S,5R)-2-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-2-yl]oxy-3-[(2R,3R,4S,5S)-4-[(2R,3R,4R,5S,6S)-4,5-dihydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-2-yl]oxy-3-hydroxy-5-(2-isothiocyanatoethylsulfanylmethyl)oxolan-2-yl]oxy-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexyl]carbamate
• CAS: 439697-28-6
• 化学式: C₅₆H₉₇N₇O₂₄S₂
• 分子量: 1316.55
• InChiKey: XVKOFUACYLTEEK-OPVPAEKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  89
• 可旋转键数：
  31
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  477
• 氢给体数：
  12
• 氢受体数：
  27

反应信息

• 作为反应物：
  描述：

  neomycin thioisocyanate 、 N¹-(11-Methoxy-5,7,14-triaza-dibenzo[a,j]anthracen-6-yl)-propane-1,3-diamine 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以86%的产率得到
  参考文献：
  名称：

  结合最好的三重识别：BQQ-新霉素缀合物的合成和核酸结合

  摘要：

  报道了 BQQ-新霉素缀合物的合成。该偶联物结合了两种配体，一种已知嵌入三链体 (BQQ)，另一种已知结合在三链体沟中（新霉素）。该偶联物稳定 TAT 以及混合碱基 DNA 三链体，优于新霉素、BQQ 或两者的组合。偶联物选择性地稳定三链体（在生理盐浓度存在的情况下），配体低至 4 μM，导致 DeltaTm > 60 摄氏度。 竞争透析研究表明，药物与三链体 DNA 结合的明显偏好/双链体/单链结构上的 RNA。建模研究表明，新霉素的结构与较大的 WH (Watson-Hoogsteen) 凹槽结合，BQQ 插入三重碱基之间。

  DOI：

  10.1021/ja034241t
• 作为产物：
  描述：

  1,1′-硫代羰基二-2(1H)-吡啶酮 、 tert-butyl N-[(2R,3R,4R,5S,6S)-2-[(2S,3S,4R,5R)-2-(2-aminoethylsulfanylmethyl)-5-[(1R,2R,3S,5R,6S)-2-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-2-yl]oxy-6-hydroxy-3,5-bis[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexyl]oxy-4-hydroxyoxolan-3-yl]oxy-4,5-dihydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以60%的产率得到neomycin thioisocyanate
  参考文献：
  名称：

  氨基糖苷-DNA缀合物的合成。

  摘要：

  提出了氨基糖苷-核酸缀合物的开发。已经进行了与卡那霉素和新霉素异硫氰酸酯共价连接的DNA二聚体的合成。此类缀合物的开发将有助于将核酸的序列特异性与结合核酸靶标中氨基糖苷抗生素的静电/形状互补性相结合。

  DOI：

  10.1016/s0960-894x(02)00157-9

文献信息

• Probing the Recognition Surface of a DNA Triplex: Binding Studies with Intercalator−Neomycin Conjugates
  作者：Liang Xue、Hongjuan Xi、Sunil Kumar、David Gray、Erik Davis、Paris Hamilton、Michael Skriba、Dev P. Arya

  DOI：10.1021/bi100071j

  日期：2010.7.6

  Thermodynamic studies on the interactions between intercalator neomycin conjugates and a DNA polynucleotide triplex [poly(dA)center dot 2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide neomycin (3) and anthraquinone neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA)center dot 2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (Tm3-2) at which poly(dA)center dot 2poly(dT) dissociated into poly(dA)center dot poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator neomycin conjugates (1-4) even at a very low concentration (2 mu M). In contrast to intercalator neomycin conjugates, the increment of Tm3-2 of poly(dA)center dot 2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator neomycin conjugates (1-4) to poly(dA)center dot 2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size (similar to 7-7.5) with poly(dA)center dot 2poly(dT) as compared to neomycin (similar to 6.5). The thermodynamic parameters of these intercalator neomycin conjugates with poly(dA). 2poly(dT) were derived from an integrated van't Hoff equation using the Tm3-2 values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA)center dot 2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M-1] of 2 with poly(dA)center dot 2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA)center dot 2poly(a) was mostly enthalpy-driven and gave negative Delta C-p values. The results described here suggest that the binding affinity of intercalator neomycin conjugates for poly(dA) center dot 2poly(a) increases as a function of the surface area of the intercalator-moiety.
• Triple recognition of B-DNA
  作者：Bert Willis、Dev P. Arya

  DOI：10.1016/j.bmcl.2009.07.079

  日期：2009.9

  A novel conjugate of Hoechst 33258, pyrene and neomycin was synthesized and examined for its binding and stabilization of A-T rich DNA duplexes using spectroscopic and viscometric techniques. The conjugate, containing three well known ligands that bind nucleic acids albeit in different binding modes, was found to significantly stabilize DNA over parent conjugates containing only one or both of the other recognition elements. The study represents the first example of DNA molecular recognition capable of minor/major groove recognition in conjunction with intercalation. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of Neomycin‐DNA/Peptide Nucleic Acid Conjugates
  作者：I. Charles、Dev P. Arya

  DOI：10.1081/car-200059973

  日期：2005.3

  Syntheses of neomycin conjugates of DNA and peptide nucleic acid (PNA) is reported. The DNA and PNA conjugates were prepared by coupling neomycin isothiocyanate with the amino group of DNA/PNA in order to form a thiourea linkage. The use of neomycin isothiocyanate as an electrophilic reagent for a general route to aminoglycoside-coupled nucleic acid biopolymers is described.
• WO2007/16455
  申请人：——

  公开号：——

  公开（公告）日：——
• Reaching into the Major Groove of B-DNA:  Synthesis and Nucleic Acid Binding of a Neomycin−Hoechst 33258 Conjugate
  作者：Dev P. Arya、Bert Willis

  DOI：10.1021/ja036742k

  日期：2003.10.1

  Synthesis of a neomycin-Hoechst 33258 conjugate is reported. The conjugate combines the ligands known to selectively bind in the duplex and the triplex groove. The conjugate stabilizes DNA duplex over DNA triplex. The conjugate selectively stabilizes the DNA duplex (in the presence of salt), with as little as 2 muM of the ligand leading to a DeltaTm of 25 degrees C.