强啡肽(1-11) | 79985-34-5

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 强啡肽(1-11)
• 中文别名: 2,4,6-三甲基-苯甲基-肼
• 英文名称: dynorphin(1-11)
• 英文别名: H-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-OH；Dynorphin (1-11)；(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoic acid
• CAS: 79985-34-5
• 化学式: C₆₃H₁₀₃N₂₁O₁₃
• 分子量: 1362.64
• InChiKey: WZHQALIQGVYQGG-QFIUEGLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  97
• 可旋转键数：
  44
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  585
• 氢给体数：
  19
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  BOC-L-脯氨酸 、 BOC-L-异亮氨酸 、 N-Boc-N'-Cbz-L-赖氨酸 、 N-Boc-N'-硝基-L-精氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 强啡肽(1-11)
  参考文献：
  名称：

  Synthesis and biological activities of dynorphin A analogues with opioid antagonist properties

  摘要：

  Dynorphin A, which displays a wide variety of physiological effects, binds to opioid receptors preferentially at the kappa receptor type. kappa-selective antagonists would be very useful as pharmacological and biochemical probes to study and better understand the action of dynorphin A at its preferred receptor. However, the development of such molecules has been elusive, and very few are known at this time. Taking these features into account, we have synthesized by the solid-phase procedure several analogues of dynorphin A containing various D-amino acid substitutions. The binding properties of the peptides have been examined at three main opioid binding sites (mu, delta, and kappa) and their kappa selectivity determined. Their biological activities have been tested in three specific pharmacological assays for agonist and/or antagonist properties. Introduction of D-Trp substitution leads to analogues, in particular [D- Trp2,8,D-Pro10]-, [D-Trp5,8,D-Pro10]-, and [D-Trp2,4,8,D-Pro10]dynorphin(1-11), showing antagonist properties in the isolated rabbit vas deferens preparation, a kappa specific bioassay. The antagonism against dynorphin A is weak, as indicated by the observed Ke values (433, 199, and 293 nM, respectively), and not very selective (kappa vs. mu). Such peptide analogues derived from the endogenous ligand and endowed with antagonist properties are the first ones reported to date and could open a promising way in designing more potent and selective kappa opioid antagonists.

  DOI：

  10.1021/jm00160a019

文献信息

• Design and synthesis of highly potent and selective cyclic dynorphin A analogs. 2. New analogs
  作者：Andrew M. Kawasaki、Richard J. Knapp、Thomas H. Kramer、Amanda Walton、William S. Wire、Shinicki Hashimoto、Henry I. Yamamura、Frank Porreca、Thomas F. Burks、Victor J. Hruby

  DOI：10.1021/jm00058a012

  日期：1993.3

  We have designed and synthesized several cyclic disulfide-containing peptide analogs of dynorphin A (Dyn A) which are conformationally constrained in the putative ''address' segment of the opioid ligand. Several of these Dyn A analogs exhibit unexpected apparent 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 analogs has resulted in the kappa/mu opioid receptor ligands [L-Pen5,Cys11]Dyn A1-11-NH2 (4), [Cys5,Cys10]Dyn A1-11-NH2 (5), [Cys5,Cys9]DynA1-11-NH2(6), and [Cys4,Cys9,Arg10]DynA1-11-NH2(7). All of these analogs possess high kappa and mu opioid receptor affinities for the central receptor (guinea pig brain), but effect only weak potency at peripheral kappa and mu opioid receptors (GPI). In fact cyclic dynorphin A analog 4 shows >19 000-fold differences between central kappa opioid affinity and potency in the guinea pig ileum (GPI). Additionally analog 4 is not an antagonist in the GPI, suggesting possible receptor differences between these sites. Substitution of Tyr1 by Phe1 in the cyclic 1-11 series gave the analog [Phe1,Cys5,Cys11]Dyn A1-11-NH2 (1) that was surprisingly potent in the guinea pig brain binding assay (IC50 = 15.1 nM) at the kappa receptor, but was inactive in the GPI and mouse vas deferens bioassays. D-Ala2 and TiC4 analogs of 1 had lower affinity at brain kappa receptors and had very weak potencies in the GPI and MVD bioassays. On the other hand, [Cys6,Cys10]DynA1-11-NH2 (8), [Cys8,D-Cys13]DynA1-13-NH2 (9), [D-CyS8,D-CyS12 ]DynA1-13-NH2 (10), and [D-Pro10,Cys5, Cys13]-Dyn Al-13-NH2 (11) were surprisingly potent in the GPI bioassay, though considerable apparent selectivity for central receptors is still retained. The apparent lack of correlation between the pharmacological profiles observed in smooth muscle and in the brain binding assays, particularly with 1 and 4, may suggest the existence of different subtypes of the kappa and mu opioid receptors in the brain and peripheral systems.
• Synthesis and biological activities of dynorphin A analogues with opioid antagonist properties
  作者：Jean E. Gairin、Honore Mazarguil、Paul Alvinerie、Serge Saint-Pierre、Jean Claude Meunier、Jean Cros

  DOI：10.1021/jm00160a019

  日期：1986.10

  Dynorphin A, which displays a wide variety of physiological effects, binds to opioid receptors preferentially at the kappa receptor type. kappa-selective antagonists would be very useful as pharmacological and biochemical probes to study and better understand the action of dynorphin A at its preferred receptor. However, the development of such molecules has been elusive, and very few are known at this time. Taking these features into account, we have synthesized by the solid-phase procedure several analogues of dynorphin A containing various D-amino acid substitutions. The binding properties of the peptides have been examined at three main opioid binding sites (mu, delta, and kappa) and their kappa selectivity determined. Their biological activities have been tested in three specific pharmacological assays for agonist and/or antagonist properties. Introduction of D-Trp substitution leads to analogues, in particular [D- Trp2,8,D-Pro10]-, [D-Trp5,8,D-Pro10]-, and [D-Trp2,4,8,D-Pro10]dynorphin(1-11), showing antagonist properties in the isolated rabbit vas deferens preparation, a kappa specific bioassay. The antagonism against dynorphin A is weak, as indicated by the observed Ke values (433, 199, and 293 nM, respectively), and not very selective (kappa vs. mu). Such peptide analogues derived from the endogenous ligand and endowed with antagonist properties are the first ones reported to date and could open a promising way in designing more potent and selective kappa opioid antagonists.