Tyr-[D-Lys-Phe-Phe-Asp]-NH₂ | 1214740-33-6

• 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: Tyr-[D-Lys-Phe-Phe-Asp]-NH₂
• 英文别名: Tyr-c[D-Lys-Phe-Phe-Asp]NH₂；Tyr-c(D-Lys-Phe-Phe-Asp)-NH2；H-Tyr-D-Lys(1)-Phe-Phe-Asp(1)-NH2；(2S,5S,8S,16R)-16-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2,5-dibenzyl-3,6,10,17-tetraoxo-1,4,7,11-tetrazacycloheptadecane-8-carboxamide
• CAS: 1214740-33-6
• 化学式: C₃₇H₄₅N₇O₇
• 分子量: 699.807
• InChiKey: XGFIVOHFTMYGLC-JZVHMONDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  51
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  235
• 氢给体数：
  8
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Rink amide resin 、 BOC-L-苯丙氨酸 、 BOC-L-天门冬氨酸Β-9-芴甲氧羰酰甲酯 、 N-叔丁氧羰基-O-(2-溴苄氧羰基)-L-酪氨酸 、 N-Boc-N'-Fmoc-D-赖氨酸 N-叔丁氧羰基-N'-芴甲氧羰基-D-赖氨酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Tyr-[D-Lys-Phe-Phe-Asp]-NH₂
  参考文献：
  名称：

  Effect of 2′,6′-dimethyl-l-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs

  摘要：

  This study reports the synthesis and biological evaluation of a series of new side-chain-to-side-chain cyclized endomorphin-2 (EM-2) and morphiceptin analogs of a general structure Tyr-c(Xaa-Phe-Phe-Yaa) NH(2) or Tyr-c(Xaa-Phe-D-Pro-Yaa)NH(2), respectively, where Xaa and Yaa were L/D Asp or L/D Lys. Further modification of these analogs was achieved by introduction of 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr in position 1. Peptides were synthesized by solid phase method and cleaved from the resin by a microwave-assisted procedure.Dmt(1)-substituted analogs displayed high affinity at the mu-opioid receptors, remained intact after incubation with the rat brain homogenate and showed remarkable, long-lasting mu-opioid receptor-mediated antinociceptive activity after central, but not peripheral administration.Our results demonstrate that cyclization is a promising strategy in the development of new opioid analgesics, but further modifications are necessary to enhance the blood-brain barrier permeability. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.10.040

文献信息

• Effect of 2′,6′-dimethyl-l-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs
  作者：Jakub Fichna、Renata Perlikowska、Anna Wyrębska、Katarzyna Gach、Justyna Piekielna、Jean Claude do-Rego、Geza Toth、Alicja Kluczyk、Tomasz Janecki、Anna Janecka

  DOI：10.1016/j.bmc.2011.10.040

  日期：2011.12

  This study reports the synthesis and biological evaluation of a series of new side-chain-to-side-chain cyclized endomorphin-2 (EM-2) and morphiceptin analogs of a general structure Tyr-c(Xaa-Phe-Phe-Yaa) NH(2) or Tyr-c(Xaa-Phe-D-Pro-Yaa)NH(2), respectively, where Xaa and Yaa were L/D Asp or L/D Lys. Further modification of these analogs was achieved by introduction of 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr in position 1. Peptides were synthesized by solid phase method and cleaved from the resin by a microwave-assisted procedure.Dmt(1)-substituted analogs displayed high affinity at the mu-opioid receptors, remained intact after incubation with the rat brain homogenate and showed remarkable, long-lasting mu-opioid receptor-mediated antinociceptive activity after central, but not peripheral administration.Our results demonstrate that cyclization is a promising strategy in the development of new opioid analgesics, but further modifications are necessary to enhance the blood-brain barrier permeability. (C) 2011 Published by Elsevier Ltd.