Fmoc-β-turn-dipeptide | 149563-21-3

• 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-β-turn-dipeptide
• 英文别名: Fmoc-Btd-OH；Fmoc-BTD；Fmoc-(3s,6s,9r)-2-oxo-3-amino-7-thia-1-azabicyclo[4.3.0]nonane-9-carboxylic acid；(3R,6S,8aS)-6-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxo-2,3,6,7,8,8a-hexahydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid
• CAS: 149563-21-3
• 化学式: C₂₃H₂₂N₂O₅S
• 分子量: 438.504
• InChiKey: MWABBJIOTKTQFS-UFYCRDLUSA-N

物化性质

• 沸点：
  737.1±60.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-β-turn-dipeptide 在 二苯基磷酸 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 [(1R,4S,10S,13S,16S)-4-(3-{N'-[(4-Methoxy-phenyl)-diphenyl-methyl]-guanidino}-propyl)-2,5,8,11,20-pentaoxo-17-thia-3,6,9,12,19-pentaaza-tricyclo[11.5.2.0^16,19]icos-10-yl]-acetic acid tert-butyl ester
  参考文献：
  名称：

  含有 β-Turn 模拟物的环状 RGD 肽

  摘要：

  αVβ3 受体是整联蛋白家族的一员，与血管生成和人类肿瘤转移有关。空间筛选产生了高活性的第一代肽 c(RGDfV)，其显示出 βII'/γ-转角排列，d-Phe 位于 βII'-转角的 i+1 位置。通过结合不同的刚性构件（转角模拟物），如 (S)- 和 (R)-Gly[ANC-2]Leu 二肽、β-转角二肽 (BTD) 和 (S ,S)-spiro-Pro-Leu 部分。通过替换先导结构 c(RGDfV) 中的 d-Phe-Val 二肽引入了这些不同的 β-转角模拟物。在肽类似物 c(RGD“S-ANC”) (PA1)、c(RGD“R-ANC”) (PA2) 和 c(RGD“BTD”) (PA3) 中，转角模拟物在β-转角，而不是 Gly 占据 βII'-转角的 i+1 位置。只有 c(RGD“spiro”) PA4 导致所需的 βII'/γ-转角排列，转角基序位于 β-转角的 i+1 和

  DOI：

  10.1021/ja9608757
• 作为产物：
  描述：

  (S)-4-<2'-(Chloroformyl)ethyl>-5-oxooxazolidin-3-carbonsaeure-benzylester 在 吡啶 、 sodium hydroxide 、 氢溴酸 、 三正丁基氢锡 、 sodium carbonate 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙酸乙酯 为溶剂， 反应 145.17h， 生成 Fmoc-β-turn-dipeptide
  参考文献：
  名称：

  Cyclic Hexapeptides and Chimeric Peptides as Mimics of Tendamistat

  摘要：

  We describe the design and evaluation of structural mimics of tendamistat, a 74-residue proteinaceous inhibitor of alpha-amylase. Cyclic hexapeptides were designed in which the sequence Trp-Arg-Tyr is constrained to the i + 1 to i + 3 positions of a type I beta-turn; these compounds inhibit alpha-amylase with K-i values of 14-32 mu M, significantly more tightly than related linear tri- and hexapeptides. Incorporation of the bicyclic Nagai-Sato type II beta-turn mimic opposite the Trp-Arg-Tyr sequence in a chimeric molecule leads to a weaker inhibitor. NMR studies indicate that the desired beta-turn conformation is adopted by the cyclic hexapeptides but not by the chimeric molecule, supporting the interpretation that the former are indeed acting as small molecule mimics of tendamistat.

  DOI：

  10.1021/ja00102a008

文献信息

• Bicyclic turned dipeptide (BTD) as a β-turn mimetic; its design, synthesis and incorporation into bioactive peptides
  作者：Ukon Nagai、Kazuki Sato、Rika Nakamura、Rika Kato

  DOI：10.1016/s0040-4020(01)90216-9

  日期：1993.3

  After reviewing the development of β-turn mimetics briefly, design, synthesis and incorporation into bioactive peptides of BTD will be mentioned. The biological activity of the BTD containing peptides and synthesis of some BTD derivatives will also be described.

  在简要回顾了β-turn模拟物的发展之后，将提及BTD的设计，合成和并入BTD的生物活性肽。还将描述含BTD的肽的生物活性以及一些BTD衍生物的合成。
• Rational Design, Synthesis, and X-ray Structure of Selective Noncovalent Thrombin Inhibitors
  作者：Jürgen Wagner、Jörg Kallen、Claus Ehrhardt、Jean-Pierre Evenou、Dieter Wagner

  DOI：10.1021/jm981013e

  日期：1998.9.1

  We have designed, synthesized, and tested in vitro a novel class of noncovalent thrombin inhibitors. The main feature of these inhibitors is a 6,5-fused bicyclic core structure that fills the S2 pocket of the active site of thrombin. The bicycle introduces conformational constraint into the ligand and locks the Xaa-Pro amide bond into the desired trans configuration. Among the known ring systems, we

  我们已经设计，合成和体外测试了一类新型的非共价凝血酶抑制剂。这些抑制剂的主要特征是6,5-稠合的双环核心结构，该结构充满了凝血酶活性位点的S2口袋。自行车将构象约束引入配体中，并将​​Xaa-Pro酰胺键锁定为所需的反式构型。在已知的环系统中，我们通过分子建模选择了7-噻吩并吲哚并酮（BTD）作为我们的基本模板。分析了几个结构特征的影响：精氨酸侧链的长度，C6处的立体化学以及优化利用S3袋的重要性。最后，以2.3 A的分辨率获得了与凝血酶结合的抑制剂15的X射线晶体结构。这些设计的凝血酶抑制剂，通过高效合成制备的蛋白质显示出比胰蛋白酶和其他丝氨酸蛋白酶高的选择性。基于通过X射线晶体学获得的信息的进一步推导当然应该允许提高效力。
• Preparation of amides from acids and resin bound azides: Suppression of intramolecular lactam formation
  作者：Zhilian Tang、Jeffrey C. Pelletier

  DOI：10.1016/s0040-4039(98)00905-8

  日期：1998.7

  A new method for the formation of amides on solid phase has been developed. The procedure involves the reaction between activated acids in solution and resin bound iminophosphoranes generated from the corresponding azides and tributylphosphine. The method is particularly attractive when starting from δ azido acids since amides can form without internal cyclization to the lactam.

  已经开发了在固相上形成酰胺的新方法。该过程涉及溶液中的活化酸与由相应的叠氮化物和三丁基膦生成的树脂结合的亚氨基正膦之间的反应。当从δ叠氮酸开始时，该方法特别有吸引力，因为可以形成酰胺而没有内部环化成内酰胺。
• Conformationally Constrained CCK4 Analogues Incorporating IBTM and BTD β-Turn Mimetics
  作者：Mercedes Martín-Martínez、Natalia De la Figuera、Miriam LaTorre、M. Teresa García-López、Edurne Cenarruzabeitia、Joaquín Del Río、Rosario González-Muñiz

  DOI：10.1021/jm050689o

  日期：2005.12.1

  To test whether a turnlike arrangement is involved in the bioactive conformation of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been replaced by recognized beta-turn mimetics (2S,5S,11bR)- and (2R,5R,11bS)-2-amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred over its type II' counterpart for efficient CCK1 receptor recognition, while BTD derivatives were completely inactive. The structure-conformation-activity relationship study in the IBTM series has shown some essential requirement of these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the adoption of turnlike conformations, (b) the presence of an 1-Phe residue and a C-terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton. Moreover, the existence of pi-pi interactions between the phenyl ring of D-Phe residues and the indole ring of IBTM framework is detrimental for binding affinity. A series of potent and selective CCK1 receptor antagonists, exemplified by compounds 8a and 8b, emerges among these IBTM-containing derivatives.
• Novel Agonists and Antagonists for Human Protease Activated Receptor 2
  作者：Grant D. Barry、Jacky Y. Suen、Giang T. Le、Adam Cotterell、Robert C. Reid、David P. Fairlie

  DOI：10.1021/jm100984y

  日期：2010.10.28

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.