| 1304127-05-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 1304127-05-6
• 化学式: C₁₁₈H₂₁₀N₁₆O₅₀S₄
• 分子量: 2781.31
• InChiKey: OCJWZOBIAFNBIM-XLHVZTCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  188.0
• 可旋转键数：
  47.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  880.06
• 氢给体数：
  28.0
• 氢受体数：
  54.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 、 1,2-乙二硫醇 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.08h， 以73%的产率得到
  参考文献：
  名称：

  Neomycin−Neomycin Dimer: An All-Carbohydrate Scaffold with High Affinity for AT-Rich DNA Duplexes

  摘要：

  A dimeric neomycin-neomycin conjugate 3 with a flexible linker, 2,2'-(ethylenedioxy)bis(ethylamine), has been synthesized and characterized. Dimer 3 can selectively bind to AT-rich DNA duplexes with high affinity. Biophysical studies have been performed between 3 and different nucleic acids with varying base composition and conformation by using ITC (isothermal calorimetry), CD (circular dichroism), FID (fluorescent intercalator displacement), and UV (ultraviolet) thermal denaturation experiments. A few conclusions can be drawn from this study: (1) FIB assay with 3 and polynucleotides demonstrates the preference of 3 toward AT-rich sequences over GC-rich sequences. (2) FID assay and UV thermal denaturation experiments show that 3 has a higher affinity for the poly(dA)center dot poly(dT) DNA duplex than for the poly(dA)center dot 2poly(dT) DNA triplex. Contrary to neomycin, 3 destabilizes poly(dA)center dot 2poly(dT) triplex but stabilizes poly(dA)center dot poly(dT) duplex, suggesting the major groove as the binding site. (3) UV thermal denaturation studies and ITC experiments show that 3 stabilizes continuous AT-tract DNA better than DNA duplexes with alternating AT bases. (4) CD and FID titration studies show a DNA binding site size of 10-12 base pairs/drug, depending upon the structure/sequence of the duplex for AT-rich DNA duplexes. (5) FID and ITC titration between 3 and an intramolecular DNA duplex [d(5'-A(12)-x-T-12-3'), x = hexaethylene glycol linker] results in a binding stoichiometry of 1:1 with a binding constant similar to 10(8) M-1 at 100 mM KCl. (6) FIB assay using 3 and 512 hairpin DNA sequences that vary in their AT base content and placement also show a higher binding selectivity of 3 toward continuous AT-rich than toward DNA duplexes with alternate AT base pairs. (7) Salt-dependent studies indicate the formation of three ion pairs during binding of the DNA duplex d[5'-A(12)-x-T-12-3'] and 3. (8) ITC-derived binding constants between 3 and DNA duplexes have the following order: AT continuous, d[5'-G(3)A(5)T(5)C(3)-3'] > AT alternate, d[5'-G(3)(AT)5C3-31 > GC-rich d[5'-A(3)G(5)C(5)T(3)-3']. (9) 3 binds to the AT-tract-containing DNA duplex (B* DNA, d[5'-G(3)A(5)T(5)C(3)-3']) with 1 order of magnitude higher affinity than to a DNA duplex with alternating AT base pairs (B DNA, d[5'-G(3)(AT)(5)C-3-3']) and with almost 3 orders of magnitude higher affinity than a GC-rich DNA (A-form, d[5'-A(3)G(5)C(5)T(3)-3']).

  DOI：

  10.1021/ja108118v
• 作为产物：
  描述：

  2,2'-(ethylenedioxy)bis(ethylisothiocyanate) 、 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 吡啶 、 4-二甲氨基吡啶 作用下， 以95%的产率得到
  参考文献：
  名称：

  Neomycin−Neomycin Dimer: An All-Carbohydrate Scaffold with High Affinity for AT-Rich DNA Duplexes

  摘要：

  A dimeric neomycin-neomycin conjugate 3 with a flexible linker, 2,2'-(ethylenedioxy)bis(ethylamine), has been synthesized and characterized. Dimer 3 can selectively bind to AT-rich DNA duplexes with high affinity. Biophysical studies have been performed between 3 and different nucleic acids with varying base composition and conformation by using ITC (isothermal calorimetry), CD (circular dichroism), FID (fluorescent intercalator displacement), and UV (ultraviolet) thermal denaturation experiments. A few conclusions can be drawn from this study: (1) FIB assay with 3 and polynucleotides demonstrates the preference of 3 toward AT-rich sequences over GC-rich sequences. (2) FID assay and UV thermal denaturation experiments show that 3 has a higher affinity for the poly(dA)center dot poly(dT) DNA duplex than for the poly(dA)center dot 2poly(dT) DNA triplex. Contrary to neomycin, 3 destabilizes poly(dA)center dot 2poly(dT) triplex but stabilizes poly(dA)center dot poly(dT) duplex, suggesting the major groove as the binding site. (3) UV thermal denaturation studies and ITC experiments show that 3 stabilizes continuous AT-tract DNA better than DNA duplexes with alternating AT bases. (4) CD and FID titration studies show a DNA binding site size of 10-12 base pairs/drug, depending upon the structure/sequence of the duplex for AT-rich DNA duplexes. (5) FID and ITC titration between 3 and an intramolecular DNA duplex [d(5'-A(12)-x-T-12-3'), x = hexaethylene glycol linker] results in a binding stoichiometry of 1:1 with a binding constant similar to 10(8) M-1 at 100 mM KCl. (6) FIB assay using 3 and 512 hairpin DNA sequences that vary in their AT base content and placement also show a higher binding selectivity of 3 toward continuous AT-rich than toward DNA duplexes with alternate AT base pairs. (7) Salt-dependent studies indicate the formation of three ion pairs during binding of the DNA duplex d[5'-A(12)-x-T-12-3'] and 3. (8) ITC-derived binding constants between 3 and DNA duplexes have the following order: AT continuous, d[5'-G(3)A(5)T(5)C(3)-3'] > AT alternate, d[5'-G(3)(AT)5C3-31 > GC-rich d[5'-A(3)G(5)C(5)T(3)-3']. (9) 3 binds to the AT-tract-containing DNA duplex (B* DNA, d[5'-G(3)A(5)T(5)C(3)-3']) with 1 order of magnitude higher affinity than to a DNA duplex with alternating AT base pairs (B DNA, d[5'-G(3)(AT)(5)C-3-3']) and with almost 3 orders of magnitude higher affinity than a GC-rich DNA (A-form, d[5'-A(3)G(5)C(5)T(3)-3']).

  DOI：

  10.1021/ja108118v

文献信息

• Influence of linker length in shape recognition of B∗ DNA by dimeric aminoglycosides
  作者：Sunil Kumar、Meredith Newby Spano、Dev P. Arya

  DOI：10.1016/j.bmc.2015.04.082

  日期：2015.7

  DNA-protein recognition has shown us the importance of DNA shapes in the recognition process. Specific high-affinity targeting of DNA shapes by small molecules is desirable for many biological applications that involve regulation of DNA based processes. Here, the effect of linker length and rigidity on the affinity of a conjugated neomycin dimer for a specific DNA shape (B* form) AT-rich DNA was explored. Binding constants approximating 10(8) M (1) for optimal linker lengths of 18-19 atoms are reported herein. (C) 2015 Elsevier Ltd. All rights reserved.