3-[(4R,7S,10S,13R,16S,19S,22R)-22-Acetylamino-13-benzyl-4-carbamoyl-10-(3-guanidino-propyl)-16-(1H-imidazol-4-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexaaza-cyclotricos-19-yl]-propionic acid | 91050-38-3

• 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: 3-[(4R,7S,10S,13R,16S,19S,22R)-22-Acetylamino-13-benzyl-4-carbamoyl-10-(3-guanidino-propyl)-16-(1H-imidazol-4-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexaaza-cyclotricos-19-yl]-propionic acid
• 英文别名: Ac-Cys(1)-Glu-His-D-Phe-Arg-Trp-Cys(1)-NH2；3-[(4R,7S,10S,13R,16S,19S,22R)-22-acetamido-13-benzyl-4-carbamoyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricos-19-yl]propanoic acid
• CAS: 91050-38-3
• 化学式: C₄₅H₅₈N₁₄O₁₀S₂
• 分子量: 1019.18
• InChiKey: DCRRHKOGXQUJTJ-UFBDBFPOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  71
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  444
• 氢给体数：
  13
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  在 ammonium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 以 水 为溶剂， 反应 0.5h， 生成 3-[(4R,7S,10S,13R,16S,19S,22R)-22-Acetylamino-13-benzyl-4-carbamoyl-10-(3-guanidino-propyl)-16-(1H-imidazol-4-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexaaza-cyclotricos-19-yl]-propionic acid
  参考文献：
  名称：

  Cyclic Melanotropins. 9. 7-D-Phenylalanine Analogues of the Active-Site Sequence

  摘要：

  The cyclic melanotropin Ac-Ser1-Tyr2-Ser3-Cys4-Glu5-His6-Phe7-Arg8 -Trp9-Cys10-Lys11-Pro12-Val13-NH is a highly potent agonist as determined in several melanocyte bioassays. In linear melanotropins, a D-Phe7 substitution leads to increased potency and often prolonged biological activity. In order to determine if this substitution would have the same effect in cyclic melanotropins, we have prepared a series of these analogues. The D-Phe7-substituted cyclic melanotropins Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-10-NH2 and Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-11-NH2 were both more potent than their cyclic L-Phe7-containing counterparts in either the frog or lizard skin bioassay by more than a factor of 10. Neither peptide, however, exhibited prolongation of biological activity in either assay. Substitution of D-Phe7 into the cyclic 4-12 and 4-13 sequences led to a slight or no increase in potency in both assays relative to the L-Phe7 counterparts, but the activity of the melanotropins was ultraprolonged in each assay. Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-12-NH2 was about equipotent to Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-13-NH2, again demonstrating, as with certain linear and cyclic L-Phe7-containing melanotropins, that the C-terminal amino acid valine is not required for biological activity or for superpotency. Similar to the linear D-Phe7 analogues that possessed ultraprolonged melanotropic activity, the 4-12 and 4-13 cyclic D-Phe7 analogues also displayed the phenomenon of superagonism, which is a time-dependent increase in efficacy over that produced by an equipotent concentration of the native hormone. Cyclization of certain linear melanotropins resulted in analogues with increased resistance to biological degradation by serum enzymes or purified proteolytic enzymes. Further, incorporation of a D-Phe7 into in the cyclic analogues led to melanotropins that were totally resistant to enzymatic inactivation by trypsin.

  DOI：

  10.1021/jm50001a008