Fmoc-β-Ala-β-Ala-β-Ala-D-Phe-(Trt)Gln-(Boc)Trp-Ala-Val-Gly-OH | 1426823-76-8

• 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: Fmoc-β-Ala-β-Ala-β-Ala-D-Phe-(Trt)Gln-(Boc)Trp-Ala-Val-Gly-OH
• 英文别名: Fmoc-bAla-bAla-bAla-D-Phe-Gln(Trt)(Trt)-Trp(Boc)-Ala-Val-Gly-OH；2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[3-[3-[3-(9H-fluoren-9-ylmethoxycarbonylamino)propanoylamino]propanoylamino]propanoylamino]-3-phenylpropanoyl]amino]-5-oxo-5-(tritylamino)pentanoyl]amino]-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]acetic acid
• CAS: 1426823-76-8
• 化学式: C₈₃H₉₃N₁₁O₁₅
• 分子量: 1484.72
• InChiKey: ZNUIRUOARKVHOX-SWYAXVINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  109
• 可旋转键数：
  38
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  369
• 氢给体数：
  11
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  Fmoc-β-Ala-β-Ala-β-Ala-D-Phe-(Trt)Gln-(Boc)Trp-Ala-Val-Gly-OH 、 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Gastrin Releasing Peptide Receptor-Directed Radioligands Based on a Bombesin Antagonist: Synthesis, ¹¹¹In-Labeling, and Preclinical Profile

  摘要：

  Novel bombesin (BBN) antagonists were synthesized by coupling the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to H-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (JMV594) through linkers of increasing number of (beta Ala)(x) residues (x = 1-3). Labeling with In-111 afforded the respective radiotracers in high purity and high specific activity. Bioconjugate affinity for the gastrin releasing peptide receptor (GRPR) as determined against [I-125-Tyr(4)]BBN was high (IC50 values in the lower nanomolar range). Radioligands poorly internalized in PC-3 cells at 37 degrees C. Radiopeptides remained >60% intact 5 min after entering the bloodstream of healthy mice. After injection in SCID mice bearing human PC-3 xenografts all analogues showed high tumor uptake and rapid background clearance via the kidneys into urine. Interestingly, pancreatic uptake, albeit GRPR-specific, declined rapidly with time. In-111-DOTA-(beta Ala)(2)-JMV594 achieved the highest tumor values among the group (17.0 +/- 2.8%ID/g vs. 8-10%ID/g, respectively, at 4 h pi) indicating that the (beta Ala)(2)-linker favors in vivo interaction of radiopeptides with the GRPR.

  DOI：

  10.1021/jm301692p
• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-缬氨酸 、 Fmoc-L-丙氨酸 、 FMOC-beta-丙氨酸 、 Fmoc-N-三苯甲基-L-谷氨酰胺 、 Fmoc-D-苯丙氨酸 、 Fmoc-L-色氨酸(Boc)-OH 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Fmoc-β-Ala-β-Ala-β-Ala-D-Phe-(Trt)Gln-(Boc)Trp-Ala-Val-Gly-OH
  参考文献：
  名称：

  Gastrin Releasing Peptide Receptor-Directed Radioligands Based on a Bombesin Antagonist: Synthesis, ¹¹¹In-Labeling, and Preclinical Profile

  摘要：

  Novel bombesin (BBN) antagonists were synthesized by coupling the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to H-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (JMV594) through linkers of increasing number of (beta Ala)(x) residues (x = 1-3). Labeling with In-111 afforded the respective radiotracers in high purity and high specific activity. Bioconjugate affinity for the gastrin releasing peptide receptor (GRPR) as determined against [I-125-Tyr(4)]BBN was high (IC50 values in the lower nanomolar range). Radioligands poorly internalized in PC-3 cells at 37 degrees C. Radiopeptides remained >60% intact 5 min after entering the bloodstream of healthy mice. After injection in SCID mice bearing human PC-3 xenografts all analogues showed high tumor uptake and rapid background clearance via the kidneys into urine. Interestingly, pancreatic uptake, albeit GRPR-specific, declined rapidly with time. In-111-DOTA-(beta Ala)(2)-JMV594 achieved the highest tumor values among the group (17.0 +/- 2.8%ID/g vs. 8-10%ID/g, respectively, at 4 h pi) indicating that the (beta Ala)(2)-linker favors in vivo interaction of radiopeptides with the GRPR.

  DOI：

  10.1021/jm301692p