cyclo-[-Arg-Gly-Asp-Amp26-] | 1018496-28-0

• 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: cyclo-[-Arg-Gly-Asp-Amp26-]
• 英文别名: 2-[(1R,4S,10S,13S)-14-benzoyl-10-[3-(diaminomethylideneamino)propyl]-3,6,9,12-tetraoxo-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetic acid
• CAS: 1018496-28-0
• 化学式: C₂₄H₃₂N₈O₇
• 分子量: 544.567
• InChiKey: UIBGFNHGJUQMPO-QZWWFDLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  238
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 2-[(1R,4S,10S,13S)-10-[3-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]propyl]-14-benzoyl-3,6,9,12-tetraoxo-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetate 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 24.0h， 生成 cyclo-[-Arg-Gly-Asp-Amp26-]
  参考文献：
  名称：

  Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues

  摘要：

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.

  DOI：

  10.1021/jm701214z