2-[4-[2-[[6-[[1,5-bis[3-[(2R,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propylamino]-1,5-dioxopentan-3-yl]amino]-6-oxohexyl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid | 1339959-48-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 2-[4-[2-[[6-[[1,5-bis[3-[(2R,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propylamino]-1,5-dioxopentan-3-yl]amino]-6-oxohexyl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• CAS: 1339959-48-6
• 化学式: C₉₉H₁₃₆N₂₄O₂₂
• 分子量: 2014.32
• InChiKey: LRSGSEDMUZQVFP-OAWCADRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.7
• 重原子数：
  145
• 可旋转键数：
  43
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  684
• 氢给体数：
  21
• 氢受体数：
  28

反应信息

• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 生成 2-[4-[2-[[6-[[1,5-bis[3-[(2R,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propylamino]-1,5-dioxopentan-3-yl]amino]-6-oxohexyl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
  参考文献：
  名称：

  Design, Synthesis, and Functionalization of Dimeric Peptides Targeting Chemokine Receptor CXCR4

  摘要：

  The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C-2 symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one Ga-68 labeled compound was studied as PET tracer.

  DOI：

  10.1021/jm2009716

文献信息

• Design, Synthesis, and Functionalization of Dimeric Peptides Targeting Chemokine Receptor CXCR4
  作者：Oliver Demmer、Ingrid Dijkgraaf、Udo Schumacher、Luciana Marinelli、Sandro Cosconati、Eleni Gourni、Hans-Jürgen Wester、Horst Kessler

  DOI：10.1021/jm2009716

  日期：2011.11.10

  The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C-2 symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one Ga-68 labeled compound was studied as PET tracer.