c(Cys^5,11) Dyn A_1-11NH2 | 127103-89-3

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: c(Cys^5,11) Dyn A_1-11NH2
• 英文别名: H-Tyr-Gly-Gly-Phe-Cys-Arg-Arg-Ile-Arg-Pro-Cys-NH2；(3S,6S,9S,12S,15R,20R,23S)-15-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-6-[(2S)-butan-2-yl]-3,9,12-tris[3-(diaminomethylideneamino)propyl]-2,5,8,11,14,22-hexaoxo-17,18-dithia-1,4,7,10,13,21-hexazabicyclo[21.3.0]hexacosane-20-carboxamide
• CAS: 127103-89-3
• 化学式: C₅₇H₈₉N₂₁O₁₂S₂
• 分子量: 1324.6
• InChiKey: NTACCAONUHCRGG-QXKRRTFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  92
• 可旋转键数：
  27
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  615
• 氢给体数：
  18
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  5,Cys¹¹>Dyn A_1-11-NH2 在 potassium hexacyanoferrate(III) 作用下， 以 水 为溶剂， 反应 1.0h， 以10%的产率得到c(Cys^5,11) Dyn A_1-11NH2
  参考文献：
  名称：

  Design and synthesis of highly potent and selective cyclic dynorphin A analogs

  摘要：

  We have designed and synthesized several cyclic disulfide-containing peptide analogues of dynorphin A (Dyn A) which are conformationally constrained in the putative "address" segment of the opioid ligand. Several of these Dyn A analogues exhibit unexpected selectivities for the kappa and mu opioid receptors(s) of the central vs peripheral nervous systems. Thus, incorporation of conformational constraint in the putative "address" segment of Dyn A analogues has resulted in the kappa/mu opioid receptor ligands [Cys5,Cys11]Dyn A1-11-NH2 (1) and [Cys5,Cys11,D-Ala8]Dyn A1-11-NH2 (2), which possess high kappa and mu opioid receptor affinities centrally (guinea pig brain, GPB), but only weak activity at peripheral kappa and mu opioid receptors (guinea pig ileum, GPI). On the other hand, [Cys8,Cys13]Dyn A1-13-NH2 and [D-Cys8,D-Cys13]Dyn A1-13-NH2 (5) display high kappa potencies and selectivities at the peripheral (GPI) but not at the central (GPB) kappa opioid receptor. The lack of correlation between the pharmacological profiles observed in smooth muscle and in the brain binding assays suggests the existence of different subtypes of the kappa and mu opioid receptors in the brain and peripheral nervous systems.

  DOI：

  10.1021/jm00169a007

文献信息

• Design, Synthesis, and Biological Properties of highly Potent Cyclic Dynorphin A Analogs. Analogs Cyclized between Positions 5 and 11
  作者：Jean-Philippe Meyer、Nathan Collins、Feng-Di Lung、Peg Davis、Teresa Zalewska、Frank Porreca、Henry I. Yamamura、Victor J. Hruby

  DOI：10.1021/jm00049a010

  日期：1994.11

  We have recently reported the synthesis of several cyclic disulfide bridge-containing peptide analogues of dynorphin A (Dyn A), which were conformationally constrained in the putative address segment of the opioid ligand. Several of these analogues, bridged between positions 5 and 11 of Dyn A(1-11)-NH2, exhibited unexpected selectivities for the kappa and mu receptors of the central over the peripheral nervous systems. In order to further investigate the conformational and topographical requirements for the residues in positions 5 and 11 of these analogues, we have synthesized a systematic series of Dyn A(1-11)-NH2 analogues incorporating the sulfydryl containing amino acids L- and D-Cys and L- and D-Pen in positions 5 and 11, thus producing 16 cyclic peptides. In addition, Dyn A(1-11)-NH2, [D-Leu(5)]Dyn A(1-11)-NH2, and [D-Lys(11)]Dyn A(1-11)-NH2 were synthesized as standards. Several of these cyclic analogues, especially c[Cys(5), D-Cys(11)] Dyn A(1-11)-NH2, c[Cys(5), L- or D-Pen(11)]Dyn A(1-11)-NH2, c[Pen(5), L-Pen(11)]Dyn A(1-11)-NH2 and c[Pen(5), L- or D-Cys(11)]Dyn A(1-11)-NH2, retained the same affinity and selectivity (vs the mu and delta receptors) as the parent compound Dyn A(1-11)-NH2 in the guinea pig brain (GPB). These same analogues and most others exhibited a much lower activity in the guinea pig ileum (GPI), thus leading to centrally vs peripherally selective peptides, but showed a different structure-activity relationship than found previously. In a wider scope, this series of analogues also provided new insights into which amino acids (and their configurations) may be used in positions 5 and 11 of Dyn A analogues for high potency and good selectivity at kappa opioid receptors. The results obtained in the GPB suggest that requirements for binding are not the same for the kappa, mu, or delta central receptors.