H-D-Phe-c[Cys-Phe-D-Trp-Lys-Thr-Cys]-Thr-NH2

• 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-c[Cys-Phe-D-Trp-Lys-Thr-Cys]-Thr-NH2
• 英文别名: DPhe-c[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-NH2；cyclo(2-7)[DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr-NH2]；H-DPhe²-c[Cys³-Phe⁷-DTrp⁸-Lys⁹-Thr¹⁰-Cys¹⁴]-Thr¹⁵-NH2；OCTA；OCT-Amide；H-DPhe-c[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-NH2；(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-7-[(1R)-1-hydroxyethyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
• 化学式: C₄₉H₆₅N₁₁O₁₀S₂
• 分子量: 1032.25
• InChiKey: SGYDRBBPYPDBRO-WNIOSIORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  72
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 在 碘 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 H-D-Phe-c[Cys-Phe-D-Trp-Lys-Thr-Cys]-Thr-NH2
  参考文献：
  名称：

  Novel, Potent, and Radio-Iodinatable Somatostatin Receptor 1 (sst₁) Selective Analogues

  摘要：

  The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivity were shown to be agonists when tested functionally in a luciferase reporter gene assay. Des-AA(1,4-6,10,12,13)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (25) was radio- iodinated (I-125-25) and specifically labeled sst(1)-expressing cells and tissues. 3D NMR structures were calculated for des-AA(1,4-6,10,12,13)- [DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH2 (16), des-AA(1,2,4-6,10,12,13)-[DAgl- (NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH2 (27) in DMSO. Though the analogues have the sst(1) pharmacophore residues at the previously determined distances from each other, the positioning of the aromatic residues in 16, 23, and 27 is different from that described earlier, suggesting an induced fit mechanism for sst(1) binding of these novel, less constrained sst(1)- selective family members.

  DOI：

  10.1021/jm801314f

文献信息

• <i>N-</i>Methyl Scan of Somatostatin Octapeptide Agonists Produces Interesting Effects on Receptor Subtype Specificity
  作者：W. G. Rajeswaran、Simon J. Hocart、William A. Murphy、John E. Taylor、David H. Coy

  DOI：10.1021/jm000361p

  日期：2001.4.1

  retention of type 2 affinity despite this residue constituting the "active center" of somatostatin peptides. N-Methylation of either the N-terminal Tyr residue or of Cys(6) in the Tyr series resulted in analogues with extraordinarily high affinity for the type 3 receptor, also with a degree of specificity. N-Methylation of the peptide bond constrains the conformational space of the amino acid and eliminates

  寻找对五种受体亚型表现出选择性亲和力的生长抑素的合成类似物具有相当大的基础和治疗意义，并且已经产生了大量具有广泛结合谱的有效激动剂类似物。过去，侧链基团和肽主链的构象限制产生了最有趣的结果。在后一类中，作为本研究的一部分，我们对肽键NH基团的N-甲基化对结合亲和力的潜在影响感兴趣，因为尚未对这些肽进行系统地研究。新化学方法的帮助是在使用Boc保护的常规固相肽合成过程中引入N-Me基团。在选择的两个系列激动剂序列DPhe（5）（或Tyr（5））-c [Cys（6）-Phe（7）-DTrp（8）-Lys的相对结合亲和力上发现了许多有趣的效果（9）-Thr（10）-Cys（11）] Thr（12）-NH（2）（SRIF编号），已被五种已知的人类生长抑素受体转染并稳定表达于CHO细胞中。残基7（Phe），10（Thr），11（Cys）和12（Thr）的N-甲基化极大地破坏了所有五个受体的亲和力。D
• Synthesis of protected norcysteines for SPPS compatible with Fmoc strategy
  作者：Manoj P. Samant、Jean E. Rivier

  DOI：10.1016/j.tetlet.2007.05.082

  日期：2007.7

  We report the synthesis of racemic Alloc-Ncy(Tmob)-OH, the resolution of its methyl ester and demonstrate its application to form a norcystine bridge in octreotide-amide using the Fmoc strategy on solid phase. N-Alloc and S-Tmob protections of norcysteine (Ncy) were found to be a preferred choice for Fmoc strategy over three other protected norcysteines synthesized, that is, Fmoc-Ncy(tBu)-OH, Alloc-Ncy(tBu)-OH, and Alloc-Ncy(Trt)-OH. (C) 2007 Elsevier Ltd. All rights reserved.
• 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.
• Novel, Potent, and Radio-Iodinatable Somatostatin Receptor 1 (sst₁) Selective Analogues
  作者：Judit Erchegyi、Renzo Cescato、Christy Rani R. Grace、Beatrice Waser、Véronique Piccand、Daniel Hoyer、Roland Riek、Jean E. Rivier、Jean Claude Reubi

  DOI：10.1021/jm801314f

  日期：2009.5.14

  The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivity were shown to be agonists when tested functionally in a luciferase reporter gene assay. Des-AA(1,4-6,10,12,13)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (25) was radio- iodinated (I-125-25) and specifically labeled sst(1)-expressing cells and tissues. 3D NMR structures were calculated for des-AA(1,4-6,10,12,13)- [DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH2 (16), des-AA(1,2,4-6,10,12,13)-[DAgl- (NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH2 (27) in DMSO. Though the analogues have the sst(1) pharmacophore residues at the previously determined distances from each other, the positioning of the aromatic residues in 16, 23, and 27 is different from that described earlier, suggesting an induced fit mechanism for sst(1) binding of these novel, less constrained sst(1)- selective family members.