(2R,4S)-1-(tert-butoxycarbonyl)-4-N-(9-fluorenylmethoxycarbonyl)aminoproline | 1018332-23-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2R,4S)-1-(tert-butoxycarbonyl)-4-N-(9-fluorenylmethoxycarbonyl)aminoproline
• 英文别名: (4S)-1-(tert-butoxycarbonyl)-4-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-D-proline；N-Boc-trans-4-N-fmoc-amino-D-proline；(2R,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 1018332-23-4
• 化学式: C₂₅H₂₈N₂O₆
• 分子量: 452.507
• InChiKey: UPXRTVAIJMUAQR-YCRPNKLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4S)-1-(tert-butoxycarbonyl)-4-N-(9-fluorenylmethoxycarbonyl)aminoproline 在 劳森试剂 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.17h， 生成 tert-butyl (2R,4S)-2-carbamothioyl-4-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

  摘要：

  Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

  DOI：

  10.1021/acsmedchemlett.0c00029
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-D-脯氨酸 在 偶氮二甲酸二异丙酯 、 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 caesium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 77.5h， 生成 (2R,4S)-1-(tert-butoxycarbonyl)-4-N-(9-fluorenylmethoxycarbonyl)aminoproline
  参考文献：
  名称：

  Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

  摘要：

  Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

  DOI：

  10.1021/acsmedchemlett.0c00029

文献信息

• Integrin targeted cyclopeptide ligands, their preparation and use
  申请人：UNIVERSITA' DEGLI STUDI DI MILANO

  公开号：EP1961759A1

  公开（公告）日：2008-08-27

  The present invention relates to hybrid cyclopeptide compounds embodying pyrrolidine- or piperidine-based amino acid substructures grafted onto a RGD (-Arg-Gly-Asp-) tripeptide sequence and acting as targeting ligands towards integrin receptors, intended, for example, for the treatment of altered angiogenic phenomena or for the preparation of therapeutically and/or diagnostically useful compounds; the invention also concerns a process for the synthesis of said cyclopeptides and biologically active derivatives thereof.

  本发明涉及混合环肽化合物，该化合物体现了接枝到 RGD（-Arg-Gly-Asp-）三肽序列上的吡咯烷或哌啶基氨基酸亚结构，可作为整合素受体的靶向配体，用于治疗改变的血管生成现象或制备治疗和/或诊断有用的化合物；本发明还涉及合成所述环肽及其生物活性衍生物的工艺。
• Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues
  作者：Franca Zanardi、Paola Burreddu、Gloria Rassu、Luciana Auzzas、Lucia Battistini、Claudio Curti、Andrea Sartori、Giuseppe Nicastro、Gloria Menchi、Nicoletta Cini、Anna Bottonocetti、Silvia Raspanti、Giovanni Casiraghi

  DOI：10.1021/jm701214z

  日期：2008.3.1

  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.
• INTEGRIN TARGETED CYCLOPEPTIDE LIGANDS, THEIR PREPARATION AND USE
  申请人：Casiraghi Giovanni

  公开号：US20100093612A1

  公开（公告）日：2010-04-15

  The present invention relates to novel hybrid cyclopeptide compounds embodying pyrrolidine- or piperidine-based amino acid substructures grafted onto a RGD (-Arg-Gly-Asp-) tripeptide sequence and acting as targeting ligands towards integrin receptors, intended, for example, for the treatment of altered angiogenic phenomena or for the preparation of therapeutically and/or diagnostically useful compounds; the invention also concerns a process for the synthesis of said cyclopeptides and biologically active derivatives thereof.
• LIBRARIES OF PEPTIDE CONJUGATES AND METHODS FOR MAKING THEM
  申请人：Brust Andreas Friedrich

  公开号：US20110172126A1

  公开（公告）日：2011-07-14

  The invention relates to peptide conjugates including at least one turn inducer wherein the turn inducer comprises a 5-7 membered saturated or unsaturated nitrogen containing heterocyclic ring and methods of making the peptides. Libraries of these peptides, methods of making the libraries are also described and methods of screening the libraries for therapeutic activity are also described.
• Characterization of Specific <i>N</i>-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library
  作者：Pei-Pei Kung、Patrick Bingham、Benjamin J. Burke、Qiuxia Chen、Xuemin Cheng、Ya-Li Deng、Dengfeng Dou、Junli Feng、Gary M. Gallego、Michael R. Gehring、Stephan K. Grant、Samantha Greasley、Anthony R. Harris、Karen A. Maegley、Jordan Meier、Xiaoyun Meng、Jose L. Montano、Barry A. Morgan、Brigitte S. Naughton、Prakash B. Palde、Thomas A. Paul、Paul Richardson、Sylvie Sakata、Alex Shaginian、William K. Sonnenburg、Chakrapani Subramanyam、Sergei Timofeevski、Jinqiao Wan、Wen Yan、Albert E. Stewart

  DOI：10.1021/acsmedchemlett.0c00029

  日期：2020.6.11

  Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.