Fmoc-Tyr(PO(NMe2)2)-OH

• 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: Fmoc-Tyr(PO(NMe2)2)-OH
• 英文别名: (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4(bis(dimethylamino)phosphoryloxy)phenyl)propanoic acid；(2S)-3-[4-[bis(dimethylamino)phosphoryloxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• 化学式: C₂₈H₃₂N₃O₆P
• 分子量: 537.552
• InChiKey: WBUXJDYGAMFMPS-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Fmoc-Tyr(PO(NMe2)2)-OH 在 4-甲基哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以82%的产率得到(S)-3-(4(bis(dimethylamino)phosphoryloxy)phenyl)propanoic acid
  参考文献：
  名称：

  [EN] SITE-SPECIFIC GENERATION OF PHOSPHORYLATED TYROSINES IN PROTEINS
  [FR] GÉNÉRATION SPÉCIFIQUE DE SITES DE TYROSINES PHOSPHORYLÉES DANS DES PROTÉINES

  摘要：

  Provided herein are novel materials and methods for site-specific incorporation of phosphotyrosines into proteins. The novel methods of the invention encompass the use of a novel aminoacyl tRNA synthetase capable of charging compatible tRNAs with a phosphotyrosine precursor. The phosphotyrosine precursor is then incorporated, site-specifically, into a protein at sites where phosphotyrosine residues are desired. The phosphotyrosine precursors are subsequently treated to convert them into phosphotyrosine residues, yielding proteins with phosphotyrosines at selected sites. The scope of the invention encompasses novel aminoacyl tRNA synthetases, novel phosphotyrosine precursors, and methods of using these materials to create site-specific phosphorylated tyrosine residues in a protein.

  公开号：

  WO2018148754A1

文献信息

• Identification of Shc Src Homology 2 Domain-Binding Peptoid−Peptide Hybrids
  作者：Won Jun Choi、Sung-Eun Kim、Andrew G. Stephen、Iwona Weidlich、Alessio Giubellino、Fa Liu、Karen M. Worthy、Lakshman Bindu、Matthew J. Fivash、Marc C. Nicklaus、Donald P. Bottaro、Robert J. Fisher、Terrence R. Burke

  DOI：10.1021/jm800789h

  日期：2009.3.26

  fluorescence anisotropy (FA) competition-based Shc Src homology 2 (SH2) domain-binding was established using the high affinity fluorescein isothiocyanate (FITC) containing peptide, FITC-NH-(CH2)4-CO-pY-Q-G-L-S-amide (8; Kd = 0.35 microM). Examination of a series of open-chain bis-alkenylamide containing peptides, prepared as ring-closing metathesis precursors, showed that the highest affinities were obtained

  使用含有高亲和力异硫氰酸荧光素 (FITC) 的肽 FITC-NH-(CH2)4-CO-pY-QGLS-酰胺，建立了基于荧光各向异性 (FA) 竞争的 Shc Src 同源性 2 (SH2) 结构域结合。 8；Kd = 0.35 microM)。对一系列含开链双链烯基酰胺的肽（作为闭环复分解前体制备）的检查表明，通过用 N α 取代的 Gly (NSG)“类肽”残基替换原始 Gly 残基获得了最高的亲和力。这提供了“Ac-pY-Q-[NSG]-L-酰胺”形式的拟肽-肽杂合体。根据 NSG 取代基的不同，这些杂交中的某些表现出比含 Gly 的亲本肽 (IC50 = 248 microM) 高 40 倍的 Shc SH2 结构域结合亲和力（例如，对于 N-高烯丙基类似物 50，IC50 = 6微）。据我们所知，这项工作代表了类肽-肽杂交体在 SH2 结构域结合拮抗剂设计中应用的第一个成功例子。这些结果可为
• Azobenzene-Based ω-Amino Acids and Related Building Blocks: Synthesis, Properties, and Application in Peptide Chemistry
  作者：Karola Rück-Braun、Stefan Kempa、Beate Priewisch、Anja Richter、Sabine Seedorff、Lukas Wallach

  DOI：10.1055/s-0029-1217074

  日期：——

  from the literature-known ω-amino acids 4,4′-APB 1a and 4,4′-AMPB 2a, meta-substituted analogues were synthesized for the incorporation into peptides and proteins. While 4,4′-APB 1a requires special chemistry for peptide synthesis, an Fmoc/t-Bu protecting group strategy is applicable for 3,3′-APB 1b. The versatility of this and other novel azobenzene ω-amino acids is demonstrated by the preparation

  偶氮苯被广泛用作光敏材料开发的光引发剂。从文献已知的ω-氨基酸4,4'-APB 1a和4,4'-AMPB 2a开始，合成了间位取代的类似物，用于掺入肽和蛋白质。虽然4,4'-APB 1a需要特殊的化学合成肽，但Fmoc / t- Bu保护基策略适用于3,3'-APB 1b。通过制备具有结合基序pTyr-Val-Asn-Val的环状可光转换磷酸肽，证明了这种和其他新颖的偶氮苯ω-氨基酸的多功能性。还介绍了偶氮亚基和相应肽的光致变色性质。 偶氮化合物-氨基酸-肽-光开关-光致变色
• A phosphoarginine containing peptide as an artificial SH2 ligand
  作者：Frank T. Hofmann、Claudia Lindemann、Helen Salia、Philipp Adamitzki、John Karanicolas、Florian P. Seebeck

  DOI：10.1039/c1cc13341a

  日期：——

  We have developed a synthesis of phosphoarginine containing peptides using a bis(2,2,2-trichloroethyl) protected phosphoarginine derivative as building block. Binding studies and computer modelling demonstrate the ability of the SH2 domain from Src kinase to recognize a phosphoarginine-containing peptide in a phosphoryl group-dependent manner.

  我们以一种双（2,2,2-三氯乙基）保护的磷精氨酸衍生物为结构单元，开发了一种含磷精氨酸肽的合成方法。结合研究和计算机建模表明，Src 激酶的 SH2 结构域能够以依赖磷酸基团的方式识别含磷精氨酸的多肽。
• N→O-Acyl shift in Fmoc-based synthesis of phosphopeptides
  作者：Hendrik Eberhard、Oliver Seitz

  DOI：10.1039/b718568e

  日期：——

  Synthetic phosphopeptides are frequently used as chemical probes to explore protein–protein interactions involved in cellular signal transduction. Most commonly, the solid-phase synthesis of phosphotyrosine-containing peptides is performed by applying the Fmoc-strategy and N-Fmoc-protected tyrosine derivatives bearing acid-labile phospho protecting groups. We observed a side-reaction, the isomerisation at threonine, which furnishes depsipeptides. It is shown that the rate of N→O-acyl migration depends on the sequence context. Depsipeptides were formed most rapidly when the phosphotyrosine was located in the +2 position. Furthermore, different phosphotyrosine building blocks were compared and a suitable method that provides phosphopeptides in enhanced purity and yield is suggested.

  合成磷酸肽经常被用作化学探针，用于探索细胞信号传导过程中蛋白质与蛋白质之间的相互作用。含磷酪氨酸肽的固相合成最常见的方法是采用 Fmoc 策略和 N-Fmoc 保护的酪氨酸衍生物，这些衍生物带有酸性可耐受的磷酸保护基团。我们观察到一个副反应，即苏氨酸处的异构化反应，它产生了去肽。研究表明，NâO-酰基迁移的速度取决于序列背景。当磷酸酪氨酸位于 +2 位时，形成去肽的速度最快。此外，研究人员还比较了不同的磷酸酪氨酸结构单元，并提出了一种能提高磷酸肽纯度和产量的合适方法。
• <i>N</i>,<i>N</i>′-Dialkyldiamide-Type Phosphate Protecting Groups for Fmoc Synthesis of Phosphotyrosine-Containing Peptides: Optimization of the Alkyl Group
  作者：Masaaki Ueki、Mitsutaka Goto、Jin Okumura、Yusuke Ishii

  DOI：10.1246/bcsj.71.1887

  日期：1998.8

  Synthesis and evaluation of three Fmoc–phosphotyrosine derivatives with a phosphate group protected as N,N′-dialkyldiamide (alkyl = Prn, Pri, and Bui) were studied. All the derivatives were obtained as crystals, among which the Buiderivative (4c) was the best in ease of preparation and excellence in cleavage property. Solid phase synthesis of a methionine-containing peptide, H–Tyr(PO3H2)–Val–Pro–Met–Leu–OH

  研究了三种 Fmoc-磷酸酪氨酸衍生物的合成和评估，其中磷酸基团被保护为 N,N'-二烷基二酰胺（烷基 = Prn、Pri 和 Bui）。所有衍生物均以晶体形式获得，其中以合成衍生物(4c)的制备容易性和裂解性能最好。含甲硫氨酸的肽 H-Tyr(PO3H2)-Val-Pro-Met-Leu-OH 的固相合成可以毫无问题地完成。