Boc-Aib-Aib-OMe | 78375-45-8

• 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: Boc-Aib-Aib-OMe
• 英文别名: methyl 2-methyl-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoate
• CAS: 78375-45-8
• 化学式: C₁₄H₂₆N₂O₅
• mdl: MFCD24392136
• 分子量: 302.371
• InChiKey: VYDUMGJTJHWTQL-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C
• 沸点：
  429.3±25.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.785
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Aib-Aib-OMe 在 4-二甲氨基吡啶 、 lithium hydroxide 、 正丁基锂 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 7.0h， 生成 tert-butyl N-[1-[[1-[[1-[(2R,3S,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

  摘要：

  N-4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of am-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N-4 prevented nonspecific proteolytic cleavage in biological medium. Aln-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N-4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N-4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00153-8
• 作为产物：
  描述：

  氟甲酸叔丁酯 在 sodium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 Boc-Aib-Aib-OMe
  参考文献：
  名称：

  PyBOP® and PyBroP: Two reagents for the difficult coupling of the α,α-dialkyl amino acid, Aib.

  摘要：

  The difficult coupling of alpha-aminoisobutyric acid (Aib) was carried out using PyBOP(R) and PyBroP in a comparative study with BOP and BroP. These reagents gave good results under simple conditions (one pot, r.t., 1 h). Coded amino acids could be coupled with Aib using PyBOP under standard conditions of peptide synthesis without racemization whereas the coupling of two Aib residues required PyBroP/DMAP. A fragment containing an Aib C-terminal could be coupled without epimerization of the penultimate residue.

  DOI：

  10.1016/s0040-4020(01)80922-4

文献信息

• Efficient coupling of α,α-dimethyl amino acid using a new chloro imidazolidium reagent, CIP
  作者：Kenichi Akaji、Naohiro Kuriyama、Yoshiaki Kiso

  DOI：10.1016/s0040-4039(00)76895-x

  日期：1994.5

  CIP (2-chloro- 1,3-dimethylimidazolidium hexafluorophosphate) was an efficient coupling agent for Nα-protected a-aminoisobutyric acid (Aib) in the presence of an additive. The reactivity was enhanced markedly by a catalytic amount of additive in the order of HOAt∼HODhbt > DMAP> HOBt. These couplings occurred without detectable racemization.

  CIP（2-氯-1,3- dimethylimidazolidium六氟磷酸盐）是一种有效的偶联剂对于N α -保护的一个在添加剂的存在下氨基异丁酸（Aib）。催化剂量按HOAt〜HODhbt> DMAP> HOBt的顺序显着提高了反应性。这些偶联发生时没有可检测的消旋作用。
• Stapling of a 3₁₀-Helix with Click Chemistry
  作者：Øyvind Jacobsen、Hiroaki Maekawa、Nien-Hui Ge、Carl Henrik Görbitz、Pål Rongved、Ole Petter Ottersen、Mahmood Amiry-Moghaddam、Jo Klaveness

  DOI：10.1021/jo101670a

  日期：2011.3.4

  short peptides that has shown promise when applied to 310- and α-helical peptides. However, atomic resolution structural information on the effect of side chain-to-side chain cyclization in 310-helical peptides is scarce, and reported data suggest that there is significant potential for improvement of existing methodologies. Here, we report a novel stapling methodology for 310-helical peptides using

  短肽在药物发现和化学生物学中作为先导化合物和分子探针很重要，但是它们众所周知的缺点（例如高构象柔韧性，蛋白酶不稳定性，生物利用度差和体内半衰期短）阻碍了它们的潜力被充分利用。实现。侧链对侧链的环化，例如通过闭合烯烃复分解（称为钉合），是增加短肽的生物活性的一种方法，当应用于3 10和α-螺旋肽时，该方法已显示出希望。然而，关于原子分辨率结构信息，有关侧链对侧链环化在3 10中的作用-螺旋肽是稀缺的，报道的数据表明，改进现有方法学的潜力很大。在这里，我们报告了一种新型的吻合方法，用于在模型氨基异丁酸（Aib）丰富的肽中使用铜（I）催化的叠氮化物-炔烃环加成（CuAAC）反应的3个10螺旋肽，并研究了侧链至NMR，X射线衍射，线性IR和飞秒2D IR光谱分析侧链环化。我们的数据表明，所得环肽比其无环前体和迄今报道的其他钉合3 10-螺旋肽代表更理想的3 10-螺旋。当应用于3 10时，由CuA
• Peptides
  申请人：Jacobsen Øyvind

  公开号：US09227995B2

  公开（公告）日：2016-01-05

  A peptide which can adopt a 310-helical conformation in which the side chains of two amino acid residues in the peptide backbone are linked by a group comprising an aromatic 5-membered ring.

  一种肽，可以在其中两个氨基酸残基的侧链由包含芳香5元环的基团连接的310螺旋构象。
• Homochiral and heterochiral associations observed in crystals of ArSO₂-(Aib)₅-OMe
  作者：Hidemasa Hikawa、Ayaka Takahashi、Shoko Kikkawa、Ayaka Suzuki、Yoshiki Takahashi、Naruka Sato、Misaki Okayasu、Isao Azumaya

  DOI：10.1039/d0ce01267j

  日期：——

  The molecular conformations, packing structures and intermolecular interactions of homopentapeptides from achiral α-aminoisobutyric acid (Aib), ArSO2-(Aib)5-OMe (Ar = p-tolyl, p-bromophenyl and p-methoxyphenyl), have been investigated by single-crystal X-ray diffraction analysis. The peptides were folded in 310-helical conformations consisting of two or three consecutive ten-atom intramolecular hydrogen-bonded

  通过非手性α-氨基异丁酸（Aib），ArSO 2-（Aib）5 -OMe（Ar =对甲苯基，对溴苯基和对甲氧基苯基）的同五肽的分子构象，堆积结构和分子间相互作用单晶X射线衍射分析。将肽折叠成3个10螺旋构象，该构象由两个或三个连续的III型或III'型十原子分子内氢键合的β-转角组成。在打包模式下，左手（M）和右手（P）3 10-螺旋分子形成具有头尾型分子间氢键的线性网络结构。根据功能基团或取代基的不同，获得了两种由同手性序列（⋯ M ⋯ M ⋯ M ⋯或⋯ P ⋯ P ⋯ P ⋯）和杂手性序列（⋯ M ⋯ P ⋯ M ⋯ P consisting）组成的网络结构。肽。有趣的是，当使用不同的结晶介质时，具有对甲苯基的肽1a结晶不同。
• Chain length effects on helix-hairpin distribution in short peptides with Aib-DAla and Aib-Aib Segments
  作者：Appavu Rajagopal、Subrayashastry Aravinda、Srinivasarao Raghothama、Narayanaswamy Shamala、Padmanabhan Balaram

  DOI：10.1002/bip.21613

  日期：——

  Boc‐Val‐Aib‐DAla‐Leu‐NHMe (3) adopts a novel α‐turn conformation, stabilized by three intramolecular hydrogen bonds (two 4→1 and one 5→1). The Aib‐DAla segment adopts a type‐I′ β‐turn conformation. The observation of an NOE between Val (1) NH↔HNCH3 (5) in CD3OH suggests, that the solid state conformation is maintained in methanol solutions. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 744–756

  Aib- D Ala二肽片段倾向于形成I'/ III'型和I / III型β-转角。素数匝的出现促进了β-发夹构象的形成，而I / III型匝可以使螺旋形成成核。八肽Boc-Leu-Phe-Val-Aib- D Ala-Leu-Phe-Val-OMe（1）先前已显示在结晶状态和溶液中形成β-发夹。使用该模型肽的Boc-PHE-VAL-AIB-XXX-LEU-PHE-NHMe（已经被检查序列截短的影响2，6），将Boc-VAL-AIB-XXX-LEU-NHMe（3，7），和Boc-AIB-XXX-NHMe（4，8），其中Xxx = d喂喂 对于具有中央Aib‐Aib节段的肽，Boc‐Phe‐Val‐Aib‐Aib‐Leu‐Phe‐NHMe（6），Boc‐Val‐Aib‐Aib‐Leu‐NHMe（7）和Boc‐Aib‐Aib‐Ben NHMe（8）螺旋构象已通过NMR研究在氢键（CD 3 OH）和非氢键（CDCl