(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-[4-[[1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]triazol-4-yl]methoxy]phenyl]propan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide | 1558028-98-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-[4-[[1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]triazol-4-yl]methoxy]phenyl]propan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 1558028-98-0
• 化学式: C₄₄H₅₉N₁₁O₁₁
• 分子量: 918.02
• InChiKey: MZNMFJGGDGWUEZ-WJVBQHSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  66
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  371
• 氢给体数：
  12
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  1-叠氮-1-脱氧-β-D-吡喃半乳糖苷 、 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 生成 (2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-[4-[[1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]triazol-4-yl]methoxy]phenyl]propan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide
  参考文献：
  名称：

  In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt¹-DALDA Analogues

  摘要：

  In this study the mu opioid receptor (MOR) ligands DALDA (Tyr-D-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-D-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (delta opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects.

  DOI：

  10.1021/ml4004765

文献信息

• In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt¹-DALDA Analogues
  作者：Steven Ballet、Cecilia Betti、Alexandre Novoa、Csaba Tömböly、Carsten Uhd Nielsen、Hans Christian Helms、Anna Lesniak、Patrycja Kleczkowska、Nga N. Chung、Andrzej W. Lipkowski、Birger Brodin、Dirk Tourwé、Peter W. Schiller

  DOI：10.1021/ml4004765

  日期：2014.4.10

  In this study the mu opioid receptor (MOR) ligands DALDA (Tyr-D-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-D-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (delta opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects.