(4S)-4-[[(2R)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3,4-dihydro-1H-naphthalene-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2S,3S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid | 188259-21-4

• 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: (4S)-4-[[(2R)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3,4-dihydro-1H-naphthalene-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2S,3S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
• CAS: 188259-21-4
• 化学式: C₄₂H₆₀N₈O₁₀
• 分子量: 836.986
• InChiKey: SCAQEXMVOPQFKF-JMGNLWMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  60
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  301
• 氢给体数：
  10
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (4S)-4-[[(2R)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3,4-dihydro-1H-naphthalene-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2S,3S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid 在 Na₂HPO₄ buffer 、 chloroamine-T 、 sodium iodide 作用下， 以47%的产率得到
  参考文献：
  名称：

  Tritiated deltorphin analogues with high specific radioactivity and high affinity and selectivity for delta opioid receptors

  摘要：

  New conformationally constrained deltorphin I and II analogues were designed and synthesized, using a more lipophilic amino acid (Ile) instead of Val at positions 5 and 6, and 2-aminotetralin-2-carboxylic acid (Ate) at position 3. Two analogues (Tyr-D-Ala-(S)-Atc-Asp-Ile-lle-Gly-NH2 and Tyr-D-Ala-(R)-Atc-Glu-Ile-IIe-Gly-NH2) with high potency and selectivity for 6 opioid receptors were chosen for tritiation, with 3,5-I-2-Tyr(1)-deltorphin analogues as precursors. Catalytic dehalotritiation of these precursors resulted in tritiated peptides with high specific radioactivity (1.28 TBq/mmol (34.5 Ci/mmol) and 1.33 TBq/mmol(36.0 Ci/mmol), respectively).

  DOI：

  10.1002/(sici)1099-1344(199710)39:10<817::aid-jlcr28>3.0.co;2-b
• 作为产物：
  描述：

  BOC-甘氨酸 、 BOC-D-丙氨酸 、 N-叔丁氧羰基-L-谷氨酸 5-苄酯 、 (R)-2-((tert-Butoxycarbonyl)amino)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 (4S)-4-[[(2R)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3,4-dihydro-1H-naphthalene-2-carbonyl]amino]-5-[[(2S,3S)-1-[[(2S,3S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Tritiated deltorphin analogues with high specific radioactivity and high affinity and selectivity for delta opioid receptors

  摘要：

  New conformationally constrained deltorphin I and II analogues were designed and synthesized, using a more lipophilic amino acid (Ile) instead of Val at positions 5 and 6, and 2-aminotetralin-2-carboxylic acid (Ate) at position 3. Two analogues (Tyr-D-Ala-(S)-Atc-Asp-Ile-lle-Gly-NH2 and Tyr-D-Ala-(R)-Atc-Glu-Ile-IIe-Gly-NH2) with high potency and selectivity for 6 opioid receptors were chosen for tritiation, with 3,5-I-2-Tyr(1)-deltorphin analogues as precursors. Catalytic dehalotritiation of these precursors resulted in tritiated peptides with high specific radioactivity (1.28 TBq/mmol (34.5 Ci/mmol) and 1.33 TBq/mmol(36.0 Ci/mmol), respectively).

  DOI：

  10.1002/(sici)1099-1344(199710)39:10<817::aid-jlcr28>3.0.co;2-b

文献信息

• Conformationally Constrained Deltorphin Analogs with 2-Aminotetralin-2-Carboxylic Acid in Position 3
  作者：Géza Tóth、Zsuzsa Darula、Antal Péter、Ferenc Fülöp、Dirk Tourwé、Hendrika Jaspers、Patricia Verheyden、Zsolt Böcskey、Zoltán Tóth、Anna Borsodi

  DOI：10.1021/jm9602726

  日期：1997.3.1

  in which selective tritiated opioid ligands were used. (R)- and (S)-Atc-deltoriphins exhibited similar Ki values in the binding assay, with almost complete loss of the stereospecificity of the binding. Conformational studies provided evidence for the little disturbance of the backbone conformational equilibrium when Phe3 is replaced by (S)- or (R)-Atc. The use of the Atc constraint gives additional evidence

  设计高活性和高度选择性δ阿片类肽的两种方法被用于获得具有改变的疏水和立体电子性质的新deltorPIn类似物。合成了Deltorphin I和II类似物，涉及在地址域的5和6位上用Ile代替Val取代，在信息域用2-氨基四氢-2-羧酸（Atc）代替Phe。肽在MVD分析中为亚纳摩尔范围内的激动剂，在GPI分析中为微摩尔或更高范围内的激动剂，显示出对delta受体的选择性非常高。在使用选择性tri化的阿片样物质配体的放射性受体结合试验中可以观察到非常相似的趋势。（R）-和（S）-Atc-deltoriphins在结合试验中显示出相似的Ki值，几乎完全丧失了结合的立体特异性。构象研究提供了证据，证明当Phe3被（S）-或（R）-Atc取代时，骨架构象平衡几乎没有受到干扰。Atc约束的使用提供了额外的证据，表明在与delta受体相互作用期间，残基3的侧链在chi 1处采用反式构象。