(4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-3-甲基-1-氧代丁基]-2,2-二甲基-4-恶唑烷羧酸 | 186023-49-4

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 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: (4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-3-甲基-1-氧代丁基]-2,2-二甲基-4-恶唑烷羧酸
• 英文名称: Fmoc-Val-Ser(ΨMe,Me-pro)-OH
• 英文别名: Fmoc-Val-Ser(Psime,Mepro)-OH；(4S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid
• CAS: 186023-49-4
• 化学式: C₂₆H₃₀N₂O₆
• 分子量: 466.534
• InChiKey: KLYUTTJBDDHKOC-VXKWHMMOSA-N

物化性质

• 沸点：
  688.6±55.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• WGK Germany：
  2

制备方法与用途

生物活性

Fmoc-Val-Ser(psi(Me,Me)pro)-OH是一种二肽。

反应信息

• 作为反应物：
  描述：

  (4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-3-甲基-1-氧代丁基]-2,2-二甲基-4-恶唑烷羧酸 在 trityl chloride polystyrene resin 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以110 mg的产率得到NH2-Val-Ser(ψ-Me,Mepro)-Val-Ser(ψ-Me,Mepro)-OH
  参考文献：
  名称：

  Synthesis of All-l Cyclic Tetrapeptides Using Pseudoprolines as Removable Turn Inducers

  摘要：

  Cyclic tetrapeptides h we generated great interest because of their broad-ranging biological properties. In order to synthesize these highly strained 12-membered cyclic compounds, a cyclization strategy using pseudoprolines as removable turn inducers has been developed. The pseudoproline derivatives induce a cisoid amide bond in the linear peptide backbone which facilitates cyclization. After cyclization, the turn inducers can be readily removed to afford cyclic tetrapeptides containing serine or threonine residues.

  DOI：

  10.1021/ol101018w
• 作为产物：
  描述：

  L-丝氨酸,N-[(9H-芴-9-基甲氧基)羰基]-L-缬氨酰-,苯基甲基酯 在 palladium on activated charcoal 氢气 、 4-甲基苯磺酸吡啶 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 15.0h， 生成 (4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-3-甲基-1-氧代丁基]-2,2-二甲基-4-恶唑烷羧酸
  参考文献：
  名称：

  Pseudo-Prolines as a Molecular Hinge:  Reversible Induction of cis Amide Bonds into Peptide Backbones

  摘要：

  Serine, threonine-derived (4S)-oxazolidine-4-carboxylic acid, and cysteine-derived (4R)-thiazolidinecarboxylic acid, denoted pseudo-proline (Xaa[Psi(R1,R2)pro]), serve as structure disrupting, solubilizing building blocks in peptide synthesis. Variation of the 2-C substituents within the heterocyclic system results in different physicochemical and conformational properties. NMR studies of a series of pseudo-proline (Psi Pro)-containing peptides reveal a pronounced effect of the 2-C substituents upon the cis to trans ratio of the adjacent amide bond in solution. 2-C unsubstituted systems show a preference similar to that of the proline residue for the trans form, whereas 2,2-dimethylated derivatives adopt the cis amide conformation in high content. For 2-monosubstituted Psi Pro, the cis-trans distribution depends on the 2-C chirality. For the 2-(S)-diastereoisomer, both forms are similarly populated in solution, whereas the 2-(R)-epimer adopts preferentially the trans form. The results are supported by conformational energy calculations and suggest that, by tailoring the degree of substitution, pseudo-prolines may serve as a temporary proline mimetic or as a hinge in peptide backbones.

  DOI：

  10.1021/ja962780a

文献信息

• Structure−Activity Relationship Studies for the Peptide Portion of the Bladder Epithelial Cell Antiproliferative Factor from Interstitial Cystitis Patients
  作者：Piotr Kaczmarek、Susan K. Keay、Gillian M. Tocci、Kristopher R. Koch、Chen-Ou Zhang、Joseph J. Barchi、David Grkovic、Li Guo、Christopher J. Michejda

  DOI：10.1021/jm8002763

  日期：2008.10.9

  We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelia] and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase methods using standard Fmoc chemistry and purified by RP-HPLC; all intermediate and final products were verified by HPLC-MS and NMR analyses. Antiproliferative activity of each derivative was determined by inhibition of (3)H-thymidine incorporation in primary normal human bladder epithelial cells. Structural components of the peptide segment of APF that proved to be important for biological activity included the presence of at least eight of the nine N-terminal amino acids, a negative charge in the C-terminal amino acid, a free amino group at the N-terminus, maintenance of a specific amino acid sequence in the C-terminal tail, and trans conformation for the peptide bonds. These data provide critical guidelines for optimization of structure in design of APF analogues as potential therapeutic agents.
• A Versatile Amino Acid Analogue of the Solvatochromic Fluorophore 4-<i>N,N</i>-Dimethylamino-1,8-naphthalimide: A Powerful Tool for the Study of Dynamic Protein Interactions
  作者：Galen Loving、Barbara Imperiali

  DOI：10.1021/ja804754y

  日期：2008.10.15

  We have developed a new unnatural amino acid based on the solvatochromic fluorophore 4-N,N-dimethylamino-1,8-naphthalimide (4-DMN) for application in the study of protein-protein interactions. The fluorescence quantum yield of this chromophore is highly sensitive to changes in the local solvent environment, demonstrating "switch-like" emission properties characteristic of the dimethylaminophthalimide family of fluorophores. In particular, this new species possesses a number of significant advantages over related fluorophores, including greater chemical stability under a wide range of conditions, a longer wavelength of excitation (408 nm), and improved synthetic accessibility. This amino acid has been prepared as an Fmoc-protected building block and may readily be incorporated into peptides via standard solid-phase peptide synthesis. A series of comparative studies are presented to demonstrate the advantageous properties of the 4-DMN amino acid relative to those of the previously reported 4-N,N-dimethylaminoph-thalimidoalanine and 6-N,N-dimethylamino-2,3-naphthalimidoalanine amino acids. Other commercially available solvatochromic fluorophores are also include in these studies. The potential of this new probe as a tool for the study of protein-protein interactions is demonstrated by introducing it into a peptide that is recognized by calcium-activated calmodulin. The binding interaction between these two components yields an increase in fluorescence emission greater than 900-fold.
• Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides
  作者：Andrew G. Roberts、Eric V. Johnston、Jae-Hung Shieh、Joseph P. Sondey、Ronald C. Hendrickson、Malcolm A. S. Moore、Samuel J. Danishefsky

  DOI：10.1021/jacs.5b08754

  日期：2015.10.14

  Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. The chemoselective activation and coupling of C-terminal peptidyl Gly thio acids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation-desulfurization strategies. Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone.