N-(6-azidohexanoyl)-D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr-OH | 1292783-90-4

• 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: N-(6-azidohexanoyl)-D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr-OH
• CAS: 1292783-90-4
• 化学式: C₅₅H₇₃N₁₃O₁₃S₂
• 分子量: 1188.4
• InChiKey: MWXKYJJHYJWKTI-JLFBTDGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.02
• 重原子数：
  83.0
• 可旋转键数：
  24.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  421.36
• 氢给体数：
  14.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  N-(6-azidohexanoyl)-D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr-OH 、 3-(prop-2-ynyloxy) benzoic acid 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.08h， 以81%的产率得到
  参考文献：
  名称：

  间隔物对通过“ CuI-Click”和“ Sulfo-Click”连接方法合成的DOTA偶联的二聚体[Tyr3] Octreotate肽的体内特性的影响

  摘要：

  双击肿瘤：这项研究报告了[Tyr3]奥曲肽二聚体的保留时间延长，该​​二聚体是通过Cu I催化的1,3-偶极环加成反应（“铜单击”）和硫代酸/磺酰叠氮化物的组合合成的酰胺化（“磺化”），表明两个[Tyr3]奥曲肽基序之间的间隔基的修饰会影响其药代动力学特征。

  DOI：

  10.1002/cbic.201000639

文献信息

• ⁶⁴Cu-Labeled Somatostatin Analogues Conjugated with Cross-Bridged Phosphonate-Based Chelators via Strain-Promoted Click Chemistry for PET Imaging: In silico through in Vivo Studies
  作者：Zhengxin Cai、Qin Ouyang、Dexing Zeng、Kim N. Nguyen、Jalpa Modi、Lirong Wang、Alexander G. White、Buck E. Rogers、Xiang-Qun Xie、Carolyn J. Anderson

  DOI：10.1021/jm500416f

  日期：2014.7.24

  Somatostatin receptor subtype 2 (sstr2) is a G-protein-coupled receptor (GPCR) that is overexpressed in neuroendocrine tumors. The homology model of sstr2 was built and was used to aid the design of new somatostatin analogues modified with phosphonate-containing cross-bridged chelators for evaluation of using them as PET imaging radiopharmaceuticals. The new generation chelators were conjugated to Tyr(3)-octreotate (Y3-TATE) through bioorthogonal, strain-promoted alkyne azide cycloaddition (SPAAC) to form CB-TE1A1P-DBCO-Y3-TATE (AP) and CB-TE1K1P-PEG4-DBCO-Y3-TATE (KP) in improved yields compared to standard direct conjugation methods of amide bond formation. Consistent with docking studies, the clicked bioconjugates showed high binding affinities to sstr2, with K-d values ranging from 0.6 to 2.3 nM. Selected isomers of the clicked products were used in biodistribution and PET/CT imaging. Introduction of the bulky dibenzocyclooctyne group in AP decreased clearance rates from circulation. However, the additional carboxylate group and PEG linker from the KP conjugate significantly improved labeling conditions and in vivo stability of the copper complex and ameliorated the slower pharmacokinetics of the clicked somatostatin analogues.