<2,6-dimethyl-Tyr¹,D-Pen²,D-Pen⁵>enkephalin | 137666-07-0

• 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: <2,6-dimethyl-Tyr¹,D-Pen²,D-Pen⁵>enkephalin
• 英文别名: H-Tyr(2,6-diMe)-D-Pen(1)-Gly-Phe-D-Pen(1)-OH；(4S,7S,13S)-13-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
• CAS: 137666-07-0
• 化学式: C₃₂H₄₃N₅O₇S₂
• 分子量: 673.855
• InChiKey: APQOTCXUXCKVTP-LCGRTSHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  251
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 BOC-L-苯丙氨酸 、 N-Boc-2,6-二甲基-L-酪氨酸 、 N^α-Boc-(S-p-MeBzl)-D-penicillamine 生成 <2,6-dimethyl-Tyr¹,D-Pen²,D-Pen⁵>enkephalin
  参考文献：
  名称：

  Systemic analgesic activity and .delta.-opioid selectivity in [2,6-dimethyl-Tyr1, D-Pen2, D-Pen5]enkephalin

  摘要：

  The cyclic peptide [2,6-dimethyl-Tyr1,D-Pen2,D-Pen5]enkephalin (2) was synthesized by solid-phase techniques and contains the optically pure unnatural amino acid 2,6-dimethyltyrosine (DMT) as a replacement for the Tyr1 residue of [D-Pen2,D-Pen5]enkephalin (DPDPE, 1). This structural modification resulted in a 10-fold increase in the potency of 2 at the delta-opioid receptor and a 35-fold increase in potency at the mu-receptor while substantial delta-receptor selectivity was maintained. In addition, 2 was 86-fold more effective than 1 at inhibiting electrically stimulated contractions of the mouse vas deferens. In the hot plate test, 2 was 7-fold more potent than 1 after intracerebroventricular administration in the mouse. While 1 was inactive following systemic administration of doses as high as 30 mg/kg, subcutaneous administration of 2 significantly inhibited writhing with an ED50 of 2.6 mg/kg. These results demonstrate that the potency and systemic activity of DPDPE are significantly increased by replacement of Tyr1 with DMT.

  DOI：

  10.1021/jm00082a008

文献信息

• Systemic analgesic activity and .delta.-opioid selectivity in [2,6-dimethyl-Tyr1, D-Pen2, D-Pen5]enkephalin
  作者：Donald W. Hansen、Awilda Stapelfeld、Michael A. Savage、Melvin Reichman、Donna L. Hammond、Ronald C. Haaseth、Henry I. Mosberg

  DOI：10.1021/jm00082a008

  日期：1992.2

  The cyclic peptide [2,6-dimethyl-Tyr1,D-Pen2,D-Pen5]enkephalin (2) was synthesized by solid-phase techniques and contains the optically pure unnatural amino acid 2,6-dimethyltyrosine (DMT) as a replacement for the Tyr1 residue of [D-Pen2,D-Pen5]enkephalin (DPDPE, 1). This structural modification resulted in a 10-fold increase in the potency of 2 at the delta-opioid receptor and a 35-fold increase in potency at the mu-receptor while substantial delta-receptor selectivity was maintained. In addition, 2 was 86-fold more effective than 1 at inhibiting electrically stimulated contractions of the mouse vas deferens. In the hot plate test, 2 was 7-fold more potent than 1 after intracerebroventricular administration in the mouse. While 1 was inactive following systemic administration of doses as high as 30 mg/kg, subcutaneous administration of 2 significantly inhibited writhing with an ED50 of 2.6 mg/kg. These results demonstrate that the potency and systemic activity of DPDPE are significantly increased by replacement of Tyr1 with DMT.