(S)-2-((((9H-芴-9-基)甲氧基)羰基)氨基)-3-(4-((双(苄氧基)磷酰基)氧基)苯基)丙酸 | 134150-51-9

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 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
• 中文名称: (S)-2-((((9H-芴-9-基)甲氧基)羰基)氨基)-3-(4-((双(苄氧基)磷酰基)氧基)苯基)丙酸
• 中文别名: N-芴甲氧羰基-2-苄基-L-磷酸酪氨酸；N-[芴甲氧羰基]-L-酪氨酸双苄基磷酸酯；NΑ-芴甲氧羰基-O-[双(苄氧基)磷酰基]-L-酪氨酸
• 英文名称: N²-<<(9H-Fluoren-9-yl)methoxy>carbonyl>-O⁴--L-tyrosine
• 英文别名: O-[bis(benzyloxy)phosphoryl]-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-tyrosine；Fmoc-Tyr(PO3Bzl2)-OH；Fmoc-pTyr-OH；Fmoc-Tyr(OPO(OBn)₂)-OH；(2S)-3-[4-bis(phenylmethoxy)phosphoryloxyphenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 134150-51-9
• 化学式: C₃₈H₃₄NO₈P
• 分子量: 663.664
• InChiKey: JSTYRDUOBZALLV-BHVANESWSA-N

物化性质

• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-((((9H-芴-9-基)甲氧基)羰基)氨基)-3-(4-((双(苄氧基)磷酰基)氧基)苯基)丙酸 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-芴甲氧羰基-O-苄基-L-磷酸酪氨酸
  参考文献：
  名称：

  制备和使用的Ñ α -fluorenylmethoxycarbonyl- ö -dibenzylphosphono -L-酪氨酸在连续流动固相肽合成

  摘要：

  Ñ α -Fluorenylmethoxycarbonyl- ö -dibenzylphosphono-大号-酪氨酸是用于固相合成中的有用的衍生物ö -phosphotyrosine肽。

  DOI：

  10.1039/c39910000338
• 作为产物：
  描述：

  在 水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (S)-2-((((9H-芴-9-基)甲氧基)羰基)氨基)-3-(4-((双(苄氧基)磷酰基)氧基)苯基)丙酸
  参考文献：
  名称：

  Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy

  摘要：

  We report a novel series of non-peptide ligands that inhibit the growth factor receptor-bound protein 2 (Grb2)-Src homology 2 (SH2) domain binding, designed using a combined computational and NMR-driven approach. We have identified a new lead compound, in (IC50 = 56 mu M), which is cytotoxic in HER2-positive breast cancer cells and disrupts the interaction between HER2 and Grb2. Thus, In can be used as a scaffold for the development of efficient Grb2-SH2 domain binding inhibitors.

  DOI：

  10.1021/jm101478n

文献信息

• Alternative Strategies for the Fmoc Solid-Phase Synthesis ofO4-Phospho-L-tyrosine-Containing Peptides
  作者：Eric A. Kitas、Reinhard Knorr、Arnold Trzeciak、Willi Bannwarth

  DOI：10.1002/hlca.19910740621

  日期：1991.9.18

  relevant O4-phospho-L-tyrosine-containing peptides have been synthesized by either the global phosphorylation of the side-chain-unprotected L-tyrosine moiety in presynthesized resin-bound peptides or alternatively by the incorporation of suitably protected O4-phospho-L-tyrosine building blocks in the continuous-flow method of Fmoc solid-phase peptide synthesis. Different phosphate-protecting groups have

  通过预先合成的树脂结合肽中侧链未保护的L-酪氨酸部分的整体磷酸化，或者通过掺入适当保护的O，已经合成了许多具有生物学意义的含O 4-磷酸-L-酪氨酸的肽Fmoc固相肽合成的连续流方法中的4-磷酸-L-酪氨酸构建基块。已经应用了不同的磷酸盐保护基。
• The synthesis of phosphopeptides via the Bpoc-based approach
  作者：Troy J. Attard、Eric C. Reynolds、John W. Perich

  DOI：10.1039/b617699m

  日期：——

  The 2-(p-biphenylyl)-2-propyloxycarbonyl (Bpoc) group was examined as an Nα-protecting group in the stepwise assembly of the MAP Kinase ERK2 [178–188; Thr(P)183, Tyr(P)185] peptide. The mild acid deprotection of the Bpoc group permitted (i) incorporation of a fully protected phosphothreonyl derivative and (ii) a TFA-based final cleavage step. The first five C-terminal residues (184–188) were incorporated in the Fmoc mode of peptide synthesis, with all subsequent amino acids coupled as their Bpoc–Xxx–OH derivatives. The target product was obtained in high purity and yield, indicating that a Bpoc-based approach to phosphopeptide synthesis was compatible with both the acid-labile side chain protecting groups employed and Hmp–Wang resin.

  在分步组装 MAP 激酶 ERK2 [178-188; Thr(P)183, Tyr(P)185] 肽的过程中，对 2-(对联苯基)-2-丙氧基羰基 (Bpoc) 作为 Nα 保护基进行了研究。通过对 Bpoc 基团进行温和的酸性脱保护，可以(i) 加入完全保护的磷苏酰基衍生物，(ii) 进行基于反式脂肪酸的最终裂解步骤。前五个 C 端残基（184-188）以 Fmoc 多肽合成模式合成，随后的所有氨基酸均以 Bpoc-Xxx-OH 衍生物的形式连接。目标产物的纯度和产量都很高，这表明基于 Bpoc 的磷酸肽合成方法与所使用的酸性侧链保护基团和 Hmp-Wang 树脂都是兼容的。
• Protein–Ligand Interactions: Thermodynamic Effects Associated with Increasing the Length of an Alkyl Chain
  作者：James M. Myslinski、John H. Clements、John E. DeLorbe、Stephen F. Martin

  DOI：10.1021/ml400211q

  日期：2013.11.14

  Thermodynamic parameters were determined for complex formation between the Grb2 SH2 domain and tripeptides of the general form Ac-pTyr-Xaa-Asn in which the Xaa residue bears a linear alkyl chain varying in length from 1-5 carbon atoms. Binding affinity increases upon adding a methylene group to the Ala derivative, but further chain extension gives no extra enhancement in potency. The thermodynamic signatures of the ethyl and n-propyl derivatives are virtually identical as are those for the n-butyl and n-pentyl analogues. Crystallographic analysis of the complexes reveals a high degree of similarity in the structure of the domain and the bound ligands with the notable exception that there is a gauche interaction in the side chains in the bound conformations of ligands having n-propyl, n-butyl, and n-pentyl groups. However, eliminating this unfavorable interaction by introducing a Z-double bond into the side chain of the n-propyl analogue does not result in an increase in affinity. Increases in the amount of nonpolar surface that is buried upon ligand binding correlate with favorable changes in Delta H degrees, but these are usually offset by corresponding unfavorable changes in -T Delta S degrees; there is little correlation of Delta C-p with changes in the amount of buried nonpolar surface.
• Phosphotyrosine-Containing Dipeptides as High-Affinity Ligands for the p56<i>^lck</i> SH2 Domain
  作者：Montse Llinàs-Brunet、Pierre L. Beaulieu、Dale R. Cameron、Jean-Marie Ferland、Jean Gauthier、Elise Ghiro、James Gillard、Vida Gorys、Martin Poirier、Jean Rancourt、Dominik Wernic、Raj Betageri、Mario Cardozo、Scott Jakes、Suzanne Lukas、Usha Patel、John Proudfoot、Neil Moss

  DOI：10.1021/jm980612i

  日期：1999.2.1

  Src homology-2 (SH2) domains are noncatalytic motifs containing approximately 100 amino acid residues that are involved in intracellular signal transduction. The phosphotyrosine-containing tetrapeptide Ac-pYEEI binds to the SH2 domain of p.56(lck) (Lck) with an affinity of 0.1 mu M. Starting from Ac-pYEEI, we have designed potent antagonists of the Lck SH2 domain which are reduced in peptidic character and in which the three carboxyl groups have been eliminated. The two C-terminal amino acids (EI) have been replaced by benzylamine derivatives and the pY + 1 glutamic acid has been substituted with leucine. The best C-terminal fragment identified, (S)-1-(4-isopropylphenyl)ethylamine, binds to the Lck SH2 domain better than the C-terminal dipeptide EI. Molecular modeling suggests that the substituents at the 4-position of the phenyl ring occupy the pY + 3 lipophilic pocket in the SH2 domain originally occupied by the isoleucine side chain. This new series of phosphotyrosine-containing dipeptides binds to the Lck SH2 domain with potencies comparable to that of tetrapeptide 1.
• PHARMACEUTICAL COMPOSITION
  申请人：AC Immune S.A.

  公开号：EP2413957B1

  公开（公告）日：2016-07-27