(2S,4R)-H-L-Pro(4-N3)-OH | 1019849-13-8

• 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: (2S,4R)-H-L-Pro(4-N3)-OH
• 英文别名: (2S,4R)-4-azidopyrrolidine-2-carboxylic acid
• CAS: 1019849-13-8
• 化学式: C₅H₈N₄O₂
• 分子量: 156.144
• InChiKey: PPRFZPZRQYPCER-DMTCNVIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  63.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4R)-H-L-Pro(4-N3)-OH 在 3,3,3-膦三基三丙酸 、 碳酸氢钠 、 copper(II) sulfate 、 N,N-二异丙基乙胺 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 3-((2S,4R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamido)propanoic acid
  参考文献：
  名称：

  Discovery of Small-Molecule Interleukin-2 Inhibitors from a DNA-Encoded Chemical Library

  摘要：

  AbstractLibraries of chemical compounds individually coupled to encoding DNA tags (DNA‐encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high‐quality DNA‐encoded chemical library comprising 30 000 drug‐like compounds; this was screened in 170 different affinity capture experiments. High‐throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor‐associated antigen carbonic anhydrase IX (CA IX) and the pro‐inflammatory cytokine interleukin‐2 (IL‐2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL‐2 was confirmed by molecular docking. Our findings suggest that DNA‐encoded chemical libraries allow the facile identification of drug‐like ligands principally to any protein of choice, including molecules capable of disrupting high‐affinity protein–protein interactions.

  DOI：

  10.1002/chem.201200952
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸甲酯 在 sodium azide 、 水 、 三乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 (2S,4R)-H-L-Pro(4-N3)-OH
  参考文献：
  名称：

  Solid-Phase Synthesis of Smac Peptidomimetics Incorporating Triazoloprolines and Biarylalanines

  摘要：

  Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural dues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide -alkyne c-ydoadditi on and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.

  DOI：

  10.1021/co200078u

文献信息

• Functionalizable Oligoprolines as Molecular Scaffolds
  作者：Yvonne A. Nagel、Michael Kuemin、Helma Wennemers

  DOI：10.2533/chimia.2011.264

  日期：——

  Azidoproline (Azp) containing oligoprolines are conformationally well-defined, helical molecular scaffolds that allow for facile functionalization. Within this article we describe the synthesis of Azp-containing oligoprolines and different strategies to introduce functional moieties. In addition, the influence of factors such as substituents at the y-position of proline as well as functional groups at the termini on the conformational stability of the molecular scaffolds are briefly presented.
• Discovery of Small-Molecule Interleukin-2 Inhibitors from a DNA-Encoded Chemical Library
  作者：Markus Leimbacher、Yixin Zhang、Luca Mannocci、Michael Stravs、Tim Geppert、Jörg Scheuermann、Gisbert Schneider、Dario Neri

  DOI：10.1002/chem.201200952

  日期：2012.6.18

  AbstractLibraries of chemical compounds individually coupled to encoding DNA tags (DNA‐encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high‐quality DNA‐encoded chemical library comprising 30 000 drug‐like compounds; this was screened in 170 different affinity capture experiments. High‐throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor‐associated antigen carbonic anhydrase IX (CA IX) and the pro‐inflammatory cytokine interleukin‐2 (IL‐2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL‐2 was confirmed by molecular docking. Our findings suggest that DNA‐encoded chemical libraries allow the facile identification of drug‐like ligands principally to any protein of choice, including molecules capable of disrupting high‐affinity protein–protein interactions.
• Solid-Phase Synthesis of Smac Peptidomimetics Incorporating Triazoloprolines and Biarylalanines
  作者：Sebastian T. Le Quement、Mette Ishoey、Mette T. Petersen、Jacob Thastrup、Grith Hagel、Thomas E. Nielsen

  DOI：10.1021/co200078u

  日期：2011.11.14

  Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural dues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide -alkyne c-ydoadditi on and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.