Cbz-Glu(α-OBn)-Ser(OBn) | 359868-56-7

• 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: Cbz-Glu(α-OBn)-Ser(OBn)
• 英文别名: 2-benzyloxycarbonylamino-4-(1-benzyloxycarbonyl-2-hydroxyethylcarbamoyl)butyric acid benzyl ester；Cbz-gGlu(OBn)-Ser-OBn；benzyl (2S)-5-[[(2S)-3-hydroxy-1-oxo-1-phenylmethoxypropan-2-yl]amino]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoate
• CAS: 359868-56-7
• 化学式: C₃₀H₃₂N₂O₈
• 分子量: 548.593
• InChiKey: XEGOVYHLBFLTKK-UIOOFZCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Cbz-Glu(α-OBn)-Ser(OBn) 在 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成 C₃₇H₃₉N₂O₁₀P
  参考文献：
  名称：

  Spacer length effects on in vitro imaging and surface accessibility of fluorescent inhibitors of prostate specific membrane antigen

  摘要：

  Prostate-specific membrane antigen (PSMA), a type II transmembrane protein, has been becoming an active target for imaging and therapeutic applications for prostate cancer. Recently, the development of its various chemical inhibitor scaffolds has been explored to serve as carriers for therapeutic or diagnostic payloads targeted to PSMA-positive tumor cells. However, there have been few efforts to definitively determine the optimal length of linker between PSMA inhibitor cores and their payload molecules with regard to the affinity to PSMA and in vitro performance. In our present model study, three spacer-length varied fluorescent inhibitors (FAM-CTT-54, FAM-X-CTT-54 and FAM-PEG(8)-CTT-54) were synthesized, and further enzymatic inhibition studies displayed linker length-dependent changes in: inhibitory potency (IC(50) = 0.41 nM, 0.35 nM, 1.93 nM), modes of binding (reversible, slowly reversible, irreversible), respectively. Furthermore, cell-labeling imaging revealed the spacer length-related change of fluorescence intensity (FAM-X-CTT-54 > FAM-PEG(8)-CTT-54 > FAM-CTT-54). These results suggest that selection of linkers and their lengths will be important considerations in the development of next-generation prostate tumor-targeted imaging probes and therapeutic agents that specifically home to PSMA on tumor cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.115
• 作为产物：
  描述：

  Cbz-L-谷氨酸 1-苄酯 、 L-丝氨酸苄酯盐酸盐 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 以95%的产率得到Cbz-Glu(α-OBn)-Ser(OBn)
  参考文献：
  名称：

  A Rational Approach to the Design of Selective Substrates and Potent Nontransportable Inhibitors of the Excitatory Amino Acid Transporter EAAC1 (EAAT3). New Glutamate and Aspartate Analogues as Potential Neuroprotective Agents

  摘要：

  Two three-dimensional receptor interaction models for EAAT substrates and nontransportable inhibitors have been developed, and new glutamate (Glu) and aspartate (Asp) analogues have been synthesized. The analogues la and 3 represent novel lead compounds for the development of EAAT substrates and nontransportable inhibitors, selective for EAATs over iGluRs, as possible neuroprotective agents useful to minimize the progression of chronic or acute neurodegenerative diseases, The role played by the protonatable amine function in the interaction with EAATs has been discussed.

  DOI：

  10.1021/jm015509z

文献信息

• Fölsch, Acta Chemica Scandinavica (1947), 1966, vol. 20, # 2, p. 459 - 473
  作者：Fölsch

  DOI：——

  日期：——
• Avaeva,S. et al., Acta Chemica Scandinavica (1947), 1963, vol. 17, p. 2718 - 2723
  作者：Avaeva,S. et al.

  DOI：——

  日期：——
• A targeted low molecular weight near-infrared fluorescent probe for prostate cancer
  作者：Tiancheng Liu、Lisa Y. Wu、Mark R. Hopkins、Joseph K. Choi、Clifford E. Berkman

  DOI：10.1016/j.bmcl.2010.09.057

  日期：2010.12

  Prostate-specific membrane antigen (PSMA) remains an active target for imaging and therapeutic applications for prostate cancer. Although radionuclide-based imaging is generally more sensitive and also has been deeply explored, near-infrared fluorescence imaging agents are simple to prepare and compatible with long-term storage conditions. In the present study, a near-infrared fluorescent imaging probe (Cy5.5-CTT-54.2) has been developed by chemical conjugation of Cy5.5N-hydroxysuccinimide ester (Cy5.5-NHS) with a potent PSMA inhibitor CTT-54.2 (IC(50) = 144 nM). The probe displays a highly potency (IC(50) = 0.55 nM) against PSMA and has demonstrated successful application for specifically labeling PSMA-positive prostate cancer cells in both two and three-dimensional cell culture conditions. These results suggest that the potent, near-infrared Cy5.5-PSMA inhibitor conjugate may be useful for the detection of prostate tumor cells by optical in vivo imaging. (C) 2010 Elsevier Ltd. All rights reserved.
• PEPTIDOMIMETIC INHIBITORS OF PSMA
  申请人：Berkmam Clifford E.

  公开号：US20140010758A1

  公开（公告）日：2014-01-09

  Compounds of the formulae, (I), wherein each variable is as defined herein are provided which are useful in (i) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable carrier, excipient, and/or diluent; (3) methods for inhibiting or treating prostrate cancer; and (4) methods for blocking or destabilizing neovasculature of a tumor.
• US9328129B2
  申请人：——

  公开号：US9328129B2

  公开（公告）日：2016-05-03