H-D-Phe-Hcy(1)-Phe-D-Trp-Lys-Thr-Hcy(1)-Thr-NH2 | 1025721-52-1

• 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: H-D-Phe-Hcy(1)-Phe-D-Trp-Lys-Thr-Hcy(1)-Thr-NH2
• 英文别名: (5S,8S,11S,14R,17S,20S)-11-(4-aminobutyl)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-20-[[(2R)-2-amino-3-phenylpropanoyl]amino]-17-benzyl-8-[(1R)-1-hydroxyethyl]-14-(1H-indol-3-ylmethyl)-7,10,13,16,19-pentaoxo-1,2-dithia-6,9,12,15,18-pentazacyclodocosane-5-carboxamide
• CAS: 1025721-52-1
• 化学式: C₅₁H₆₉N₁₁O₁₀S₂
• 分子量: 1060.31
• InChiKey: NPEOLRRQBJZIFT-MQBKPZGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  74
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  406
• 氢给体数：
  13
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  N-Boc-O-苄基-L-苏氨酸 、 N-叔丁氧羰基-N'-(2-氯苄氧羰基)-L-赖氨酸 、 BOC-D-色氨酸 、 N-tert-butoxycarbonyl-S-p-methoxybenzyl-L-homocysteine 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 H-D-Phe-Hcy(1)-Phe-D-Trp-Lys-Thr-Hcy(1)-Thr-NH2
  参考文献：
  名称：

  Ring Size in Octreotide Amide Modulates Differently Agonist versus Antagonist Binding Affinity and Selectivity

  摘要：

  H-DPhe(2)-c[Cys(3) -Phe(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Thr(15) -NH(2) (1) (a somatostatin agonist, SRIF numbering) and H-Cpa(2) -c[DCys(3) -Tyr(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Nal(15)-NH(2) (4) (a somatostatin antagonist) are based on the structure of octreotide that binds to three somatostatin receptor subtypes (SSt(2/3/5)) with significant binding affinity. Analogues of 1 and 4 were synthesized with norcysteine (Ncy), homocysteine (Hcy), or D-homocysteine (DHcy) at positions 3 and/or 14. Introducing Ncy at positions 3 and 14 constrained the backbone flexibility, resulting in loss of binding affinity at all sst(s) The introduction of Hey at positions 3 and 14 improved selectivity for sst(2) as a result of significant loss of binding affinity at the other ssts. Substitution by DHcy at position 3 in the antagonist scaffold (5), on the other hand, resulted in a significant loss of binding affinity at sst(2) and sst(3) as compared to the different affinities of the parent compound (4). The 3D NMR structures of the analogues in dimethylsulfoxide are consistent with the observed binding affinities.

  DOI：

  10.1021/jm701445q

文献信息

• Ring Size in Octreotide Amide Modulates Differently Agonist versus Antagonist Binding Affinity and Selectivity
  作者：Christy Rani R. Grace、Judit Erchegyi、Manoj Samant、Renzo Cescato、Veronique Piccand、Roland Riek、Jean Claude Reubi、Jean E. Rivier

  DOI：10.1021/jm701445q

  日期：2008.5.1

  H-DPhe(2)-c[Cys(3) -Phe(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Thr(15) -NH(2) (1) (a somatostatin agonist, SRIF numbering) and H-Cpa(2) -c[DCys(3) -Tyr(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Nal(15)-NH(2) (4) (a somatostatin antagonist) are based on the structure of octreotide that binds to three somatostatin receptor subtypes (SSt(2/3/5)) with significant binding affinity. Analogues of 1 and 4 were synthesized with norcysteine (Ncy), homocysteine (Hcy), or D-homocysteine (DHcy) at positions 3 and/or 14. Introducing Ncy at positions 3 and 14 constrained the backbone flexibility, resulting in loss of binding affinity at all sst(s) The introduction of Hey at positions 3 and 14 improved selectivity for sst(2) as a result of significant loss of binding affinity at the other ssts. Substitution by DHcy at position 3 in the antagonist scaffold (5), on the other hand, resulted in a significant loss of binding affinity at sst(2) and sst(3) as compared to the different affinities of the parent compound (4). The 3D NMR structures of the analogues in dimethylsulfoxide are consistent with the observed binding affinities.