H-Tyr(2,6-diMe)-D-Arg-1Nal-Lys-NH2 | 1593480-45-5

• 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-Tyr(2,6-diMe)-D-Arg-1Nal-Lys-NH2
• 英文别名: (2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]hexanamide
• CAS: 1593480-45-5
• 化学式: C₃₆H₅₁N₉O₅
• 分子量: 689.858
• InChiKey: RNKFBOUNNJERAH-MBEDZMRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  50
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  267
• 氢给体数：
  9
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Fmoc-3-(1-萘基)-L-丙氨酸 、 N-芴甲氧羰基-2,6-二甲基-L-酪氨酸 、 Fmoc-Lys(Boc)-NH2 、 N’-[(2,3-二氢-2,2,4,6,7-五甲基苯并呋喃-5-基)磺酰基]-N-芴甲氧羰基-D-精氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 以170.4 mg的产率得到H-Tyr(2,6-diMe)-D-Arg-1Nal-Lys-NH2
  参考文献：
  名称：

  [Dmt1]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile

  摘要：

  Analogues of [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine), a potent mu opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe(3) with various 2',6'-dialkylated Phe analogues, including 2',6'-dimethylphenylalanine (Dmp), 2',4',6'-trimethylphenylalanine (Tmp), 2'-isopropyl-6'-methylphenylalanine (Imp) and 2'-ethyl-6'-methylphenylalanine (Emp), or with the bulky amino acids 3'-(1-naphthyl)alanine (1-Nal), 3'-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased mu agonist potency, retained mu receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp(3)-, Imp(3)-, Emp(3)- and 1-Nal(3)-containing analogues showed much increased kappa receptor binding affinity and had mixed mu/kappa properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the C-beta-C-gamma bond of the Xxx(3) residue, in correlation with the observed kappa receptor binding enhancement. Compounds with a mixed mu/kappa opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.011

文献信息

• [Dmt1]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile
  作者：Longxiang Bai、Ziyuan Li、Jiajia Chen、Nga N. Chung、Brian C. Wilkes、Tingyou Li、Peter W. Schiller

  DOI：10.1016/j.bmc.2014.02.011

  日期：2014.4

  Analogues of [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine), a potent mu opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe(3) with various 2',6'-dialkylated Phe analogues, including 2',6'-dimethylphenylalanine (Dmp), 2',4',6'-trimethylphenylalanine (Tmp), 2'-isopropyl-6'-methylphenylalanine (Imp) and 2'-ethyl-6'-methylphenylalanine (Emp), or with the bulky amino acids 3'-(1-naphthyl)alanine (1-Nal), 3'-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased mu agonist potency, retained mu receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp(3)-, Imp(3)-, Emp(3)- and 1-Nal(3)-containing analogues showed much increased kappa receptor binding affinity and had mixed mu/kappa properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the C-beta-C-gamma bond of the Xxx(3) residue, in correlation with the observed kappa receptor binding enhancement. Compounds with a mixed mu/kappa opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse. (c) 2014 Elsevier Ltd. All rights reserved.