N-(9-fluorenylmethoxycarbonyl)-(2S,4S)-4-tert-butoxyproline

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(9-fluorenylmethoxycarbonyl)-(2S,4S)-4-tert-butoxyproline
• 英文别名: Fmoc-Hyp(tBu)；Fmoc-cis-4-tert-butoxy-L-proline；Fmoc-hyp(O^tBu)-OH；(2S,4S)-4-(tert-butoxy)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidine-2-carboxylic acid；(2S,4S)-1-(9H-fluoren-9-ylmethoxycarbonyl)-4-[(2-methylpropan-2-yl)oxy]pyrrolidine-2-carboxylic acid
• 化学式: C₂₄H₂₇NO₅
• 分子量: 409.482
• InChiKey: WPBXBYOKQUEIDW-BTYIYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(9-fluorenylmethoxycarbonyl)-(2S,4S)-4-tert-butoxyproline 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 Fmoc-cis-4-hyp(OtBu)-NHMe
  参考文献：
  名称：

  Conformational Changes Associated with Post-Translational Modifications of Pro¹⁴³ in Skp1 of Dictyostelium—A Dipeptide Model System

  摘要：

  Prolyl hydroxylation and subsequent glycosylation of the E3(SCF) ubiquitin ligase subunit Skp1 affects its conformation and its interaction with F-box proteins and, ultimately, O-2-sensing in the organism. Taking a reductionist approach to understand the molecular basis for these effects, a series of end-capped Thr-Pro dipeptides was synthesized, tracking the sequential post-translational modifications that occur in the protein. The conformation of the pyrrolidine ring in each compound was gauged via coupling constants ((3)J(H alpha,H beta)) and the electronegativity of the C gamma-substituents by chemical shifts (C-13). The equilibrium between the cis-trans conformations about the central prolyl peptide bond was investigated by integration of signals corresponding to the two species in the H-1 NMR spectra over a range of temperatures. These studies revealed an increasing preference for the trans-conformation in the order Pro < Hyp < [alpha-(1,4)GlcNAc]Hyp. Rates for the forward and reverse reactions, determined by magnetization transfer experiments, demonstrated a reduced rate for the trans-to-cis conversion and a significant increase in the cis-to-trans conversion upon hydroxylation of the proline residue in the dipeptide. NOE experiments suggest that the Thr side chain pushes the sugar away from the pyrrolidine ring. These effects, which depended on the presence of the N-terminal Thr residue, offer a mechanism to explain altered properties of the corresponding full-length proteins.

  DOI：

  10.1021/ja5033277
• 作为产物：
  描述：

  (2S,4S)-1-(苄基羰基)-4-羟基吡咯烷-2-羧酸 在 potassium carbonate 、 sodium hydroxide 、 silver(l) oxide 作用下， 以 四氢呋喃 、 环己烷 、 丙酮 为溶剂， 生成 N-(9-fluorenylmethoxycarbonyl)-(2S,4S)-4-tert-butoxyproline
  参考文献：
  名称：

  通过 C4(S)-(NH2/OH/NHCHO)-L-prolyl 多肽中的侧链主链 H-键，立体依赖性和溶剂特异性形成不寻常的 β-结构

  摘要：

  结果表明，C4(S)-NH2/OH/NHCHO-脯氨酰多肽在水性介质中表现出 PPII 构象，但在相对疏水的溶剂三氟乙醇 (TFE) 中转化为不寻常的 β 结构。通过相应的 C4(S)-胍基/(NH/O)-乙酰衍生物中不存在 β-结构和在 C4(S) 中保留 β-结构证明了 H 键在定义特定结构中的立体定向作用)-(NHCHO)-脯氨酰多肽在 TFE 中。独特的构象由特征 CD 图案识别并得到拉曼光谱数据的支持。溶剂依赖性构象效应被解释为促进水中 PPII 构象的残留内 H 键合，转换为 TFE 中的链间 H 键合。

  DOI：

  10.1002/bip.22981

文献信息

• The Aberrance of the 4<i>S</i> Diastereomer of 4-Hydroxyproline
  作者：Matthew D. Shoulders、Frank W. Kotch、Amit Choudhary、Ilia A. Guzei、Ronald T. Raines

  DOI：10.1021/ja103082y

  日期：2010.8.11

  typically accompany a C(gamma)-endo ring pucker. This same transannular hydrogen bond enhances an n-->pi* interaction that stabilizes the trans conformation of the peptide bond preceding hyp, endowing hyp with the unusual combination of a C(gamma)-endo ring pucker and high trans/cis ratio. O-Methylation of hyp to form (2S,4S)-4-methoxyproline (mop) eliminates the transannular hydrogen bond and restores a prototypical

  脯氨酰 4-羟化酶在原胶原、弹性蛋白和其他蛋白质中某些 (2S)-脯氨酸 (Pro) 残基的 γ-碳原子上以 4R 构型安装羟基，形成 (2S,4R)-4-羟脯氨酸 (Hyp) ）。这种普遍存在的翻译后修饰产生的粗俗效应强化了 C(gamma)-exo 环褶皱并稳定了胶原蛋白三螺旋。尽管带负电的 4S 取代基能够增强 Pro 更常见的 C(gamma)-内环褶皱，但尚未在蛋白质中观察到 Hyp 非对映异构体 (2S,4S)-4-羟脯氨酸 (hyp)。在这里，我们利用密度泛函理论、光谱学、晶体学和量热法，利用胶原蛋白模型系统探索 hyp 掺入对蛋白质稳定性的影响。我们发现 Pro 的 4S-羟基化形成 hyp 确实强制了 C(gamma)-内环褶皱，但羟基部分和 hyp 的羰基之间的跨环氢键扭曲了通常伴随 C 的主链扭转角(gamma)-endo 环褶皱。这种相同的跨环氢键增强了 n-->pi*
• Structure–Activity Studies of Phosphopeptidomimetic Prodrugs Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3 (Stat3)
  作者：Pijus K. Mandal、Zhiyong Ren、Xiaomin Chen、Kumar Kaluarachchi、Warren S.-L. Liao、John S. McMurray

  DOI：10.1007/s10989-012-9313-0

  日期：2013.3

  4′-phosphonodifluoromethyl cinnamoyl-Haic-Gln-NHBn, appending methyl group to the β-position of the cinnamate increased potency ca. twofold, which paralleled the increase in affinity of the corresponding phosphopeptide models. However, dramatic increases in potency were observed when the C-terminal C(O)NHBn of Gln-NHBn was replaced with a simple methyl group. In this communication we continue to explore the

  信号转导和转录激活因子 3 (Stat3) 通过其 Src 同源 2 (SH2) 结构域与其受体结合，从而传输来自生长因子和白细胞介素 6 家族细胞因子的信号。这导致 Tyr705 磷酸化、二聚化、易位到细胞核和下游基因转录的调节。Stat3 在几种人类癌症中被组成型激活，并且是抗癌药物设计的目标。我们之前已经表明，靶向 SH2 结构域的磷酸肽模拟物前药可以抑制完整癌细胞中 Tyr705 的磷酸化。在由 4'-膦酰二氟甲基肉桂酰-Haic-Gln-NHBn 的双-新戊酰氧基甲酯组成的一系列前药中，将甲基附加到肉桂酸酯的 β 位可增加效力约。双重，这与相应磷酸肽模型的亲和力增加平行。然而，当 Gln-NHBn 的 C 末端 C(O)NHBn 被简单的甲基取代时，观察到效力的显着增加。在本文中，我们继续探索前药结构修饰对其抑制 Tyr705 磷酸化能力的影响。通过荧光偏振（Pro IC 在本文中，我们继续探索前药结构修饰对其抑制
• Circular dichroism studies of type III collagen mimetic peptides with anti- or pro-aggregant activities on human platelets
  作者：Julien Pêcher、Viviane Pires、Ibtissem Djaafri、Sophie Da Nascimento、Françoise Fauvel-Lafève、Chantal Legrand、Pascal Sonnet

  DOI：10.1016/j.ejmech.2008.10.026

  日期：2009.6

  We report the synthesis of collagen related peptides containing the peptide sequence Lys-Hyp-Gly-Glu-Hyp-Gly-Pro-Lys. The anti-thrombotic activity effects of different glycine mutations in this sequence were studied in regard with their different adopted conformations. The biological results could be correlated to the glycine propensity to adopt a more stable polyproline 11 helix conformation. The incorporation of these sequences in "collagen-like" a-triple-helix peptides shows a pro-thrombotic activity compared to a scrambled negative control peptide which possesses no significant activity. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Prahl; Derdowska; Dawidowska, Polish Journal of Chemistry, 2003, vol. 77, # 7, p. 881 - 887
  作者：Prahl、Derdowska、Dawidowska、Neubert、Hartrodt、Wierzba、Juzwa、Lammek

  DOI：——

  日期：——
• BICYCLIC NONANE AND DECANE COMPOUNDS HAVING DOPAMINE RECEPTOR AFFINITY
  申请人：Allelix Biopharmaceuticals Inc.

  公开号：EP0797577B1

  公开（公告）日：2000-07-26