亮氨酰脯氨酸苄酯 | 83610-64-4

• 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: 亮氨酰脯氨酸苄酯
• 英文名称: leucylproline benzyl ester
• 英文别名: Leu-Pro-OBn hydrochloride；H-Leu-Pro-OBzl；Leu-Pro-OBn；benzyl (2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidine-2-carboxylate
• CAS: 83610-64-4
• 化学式: C₁₈H₂₆N₂O₃
• 分子量: 318.416
• InChiKey: GCVOYLKIWSKHII-HOTGVXAUSA-N

物化性质

• 沸点：
  466.2±45.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  亮氨酰脯氨酸苄酯 在 palladium dihydroxide N-甲基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -5.0~20.0 ℃ 、101.33 kPa 条件下， 反应 23.0h， 生成 ((5S,8S,12S,13R,16S,17R,20S,22aS)-12-Hydroxy-5-isobutyl-8,13-diisopropyl-17,21-dimethyl-20-naphthalen-2-ylmethyl-4,7,10,15,19,22-hexaoxo-icosahydro-9,18-dioxa-3a,6,14,21-tetraaza-cyclopentacyclohenicosen-16-yl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Tamandarin B Analogues

  摘要：

  [GRAPHICS]The synthesis of two tamandarin B analogues in which the N,O-Me(2)Tyr(5) unit was replaced by N-Me-phenylaianine (N-MePhe(5)) and (S)-2(methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth(5)) is described. The choice of the macrocyclization site was crucial to achieve satisfactory macrolactamization. Coupling between norstatine (Nst(1)) and threonine (Thr(6)) afforded only a 15% yield, while lactamization between proline (Pro(4)) and the aromatic moiety could be achieved in 65% yield.

  DOI：

  10.1021/ol0530023
• 作为产物：
  描述：

  L-脯氨酸苄酯盐酸盐 在 N-甲基吗啉 、 1-羟基苯并三唑 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.67h， 生成 亮氨酰脯氨酸苄酯
  参考文献：
  名称：

  Synthesis of six common amino acid sequence fragments of thymosins .BETA.4, .BETA.8 and .BETA.9 and determination of their effects on the low E-rosette forming cells of lupus nephritis patients.

  摘要：

  胸腺素β4、β8和β9常见的六种氨基酸序列片段，即H-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-OH(第16-26位)，H-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-OH(第31-39位)，H-Asp-Lys-Pro-Asp-OH(第2-5位)，H-Phe-Asp-Lys-OH(第12-14位)，H-Leu-Pro-OH(第28-29位)和H-Glu-Ile-OH(第8-9位)，采用液相法合成，并检测它们对狼疮肾炎患者低E花环形成细胞的影响。其中两个片段，H-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-OH和H-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-OH，与患者血液在体外孵育后增加了E花环形成能力，尽管效果不如胸腺素β9，但另外四个肽片段，H-Asp-Lys-Pro-Asp-OH，H-Phe-Asp-Lys-OH，H-Leu-Pro-OH和H-Glu-Ile-OH，则没有效果。

  DOI：

  10.1248/cpb.32.228

文献信息

• Studies on Peptide Antibiotic “Gratisin”
  作者：Makoto Tamaki

  DOI：10.1246/bcsj.57.3210

  日期：1984.11

  According to a primary structure proposed for an antibiotic peptide, gratisin, four peptides containing respectively partial sequences, l-Phe–l-Pro–l-Tyr, d-Phe–l-Pro–l-Tyr, l-Phe–l-Pro–d-Tyr, and d-Phe–l-Pro–d-Tyr, were synthesized by a liquid phase method. Among them, cyclo(–l-Val–l-Orn–l-Leu–d-Phe–l-Pro–d-Tyr–)2 showed the strongest activity against the Gram-positive microorganisms tested. The activity toward Bacillus subtilis was similar to that of gramicidin S. Therefore, it is quite possible that natural gratisin is identical to this peptide. To facilitate a further investigation of the structure-activity relationship, four additional analogs were prepared. The results of their antibiotic activities showed that an interchange of d-Phe residues with d-Tyr residues caused the decrease of activity, and that the hydroxyl group of d-Tyr residues had no important role in this activity. The peptides possessing partial sequences, d-Phe–d-Tyr–l-Pro and l-Pro–d-Phe–d-Phe, exhibited strong activity. These facts show that the positions of Pro residues are not restricted to 5 and 5′ for the exhibition of the activity. The CD spectra of these synthetic peptides in an aqueous solution reflected the partial sequences around Pro residues, which affect largely the conformation of these synthetic antibiotics. The temperature dependence of these CD spectra indicated that the conformation of biologically active peptides is more stable than those of less active peptides.

  根据为抗生素多肽格拉亭拟订的一个主要结构，用液相法合成了分别含有部分序列l-苯丙–l-脯–l-酪、d-苯丙–l-脯–l-酪、l-苯丙–l-脯–d-酪和d-苯丙–l-脯–d-酪的四个多肽。其中环(–l-缬–l-鸟–l-亮–d-苯丙–l-脯–d-酪–)2 对所试的革兰氏阳性微生物表现最强的活性。它对枯草杆菌的活性与短杆菌肽 S的相似。因此，天然格拉亭与这个多肽很可能就是同一个东西。为了便于进一步探讨结构与活性关系，制备了四个别的类似物。从它们的抗生素活性的结果看出，把 d-苯丙残基换成d-酪残基会使活性降低，而 d-酪残基的羟基对此活性没有重要作用。具有部分序列 d-苯丙–d-酪–l-脯和 l-脯–d-苯丙–d-苯丙的各个多肽表现很强的活性。这些情况说明，脯残基的位置并不是非固定在5 及 5'不可才表现出活性。这些合成多肽在溶液中的圆二色性光谱反映了脯残基周围的部分序列，它们对这些合成抗生素的构象有很大影响。这些圆二色性光谱的温度依赖关系指出，有生物活性的多肽的构象比活性较小的多肽的构象更稳定些。
• Synthesis and Properties of Gramicidin S Analogs Containing Pro–D-Phe Sequence in Place of D-Phe–Pro Sequence in the β-Turn Part of the Antibiotic
  作者：Makoto Tamaki、Michiaki Takimoto、Ichiro Muramatsu

  DOI：10.1246/bcsj.58.1469

  日期：1985.5

  that of gramicidin S, and its activity toward other microorganisms tested was 1/2 that of gramicidin S. The CD spectra of these analogs and gramicidin S in an aqueous solution differ from each other, indicating that these peptides have different conformations in aqueous solutions. The CD spectrum of [L-Pro4, D-Phe5]-gramicidin S resembles a graphical average of the CD spectra of gramicidin S and [L-Pro4

  合成了两种短杆菌肽 S 类似物 [L-Pro4, D-Phe5]-短杆菌肽 S 和 [L-Pro4,4', D-Phe5,5']-短杆菌肽 S，以研究 Pro 位置之间的关系残留物、抗生素活性和 CD 谱。[L-Pro4,4', D-Phe5,5']-短杆菌肽 S 几乎没有活性。另一方面，[L-Pro4, D-Phe5]-短杆菌肽S对枯草杆菌和黄微球菌的活性与短杆菌肽S相同，对其他微生物的活性是短杆菌肽S的1/2这些类似物和短杆菌肽S在水溶液中的CD谱互不相同，说明这些肽在水溶液中具有不同的构象。[L-Pro4, D-Phe5]-短杆菌肽 S 的 CD 光谱类似于短杆菌肽 S 和 [L-Pro4,4', D-Phe5,5']-短杆菌肽 S 的 CD 光谱的图形平均值。
• Tamandarin analogs and fragments thereof and methods of making and using
  申请人：Joullie M. Madeleine

  公开号：US20070149446A1

  公开（公告）日：2007-06-28

  The present invention is directed to a compound of Formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , W, X, Y, and Z are defined herein. The compounds of the present invention are useful as anticancer agents. Specifically, the compounds are useful for treating or preventing cancer and tumor growth. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to methods of using a compound according to the above formula.

  本发明涉及公式I中R1、R2、R3、R4、R5、R6、W、X、Y和Z所定义的化合物。本发明的化合物可用作抗癌剂。具体而言，这些化合物可用于治疗或预防癌症和肿瘤生长。本发明还涉及包括上述公式中化合物的组合物。本发明还涉及使用上述公式中化合物的方法。
• Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them
  申请人：Rodriguez Ignacio

  公开号：US20080009435A1

  公开（公告）日：2008-01-10

  The invention relates to aplidine derivatives of the general formula: which are useful for the treatment of tumors.

  本发明涉及一种通式为的aplidine衍生物，其可用于治疗肿瘤。
• Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL
  作者：Lei Du、Sierrah M. Grigsby、Aihong Yao、Yujie Chang、Garrett Johnson、Haiying Sun、Zaneta Nikolovska-Coleska

  DOI：10.1021/acsmedchemlett.8b00175

  日期：2018.9.13

  MLL-fusion proteins, AF9 and ENL, play an essential role in the recruitment of DOT1L and the H3K79 hypermethylation of MLL target genes, which is pivotal for leukemogenesis. Blocking these interactions may represent a novel therapeutic approach for MLL-rearranged leukemia. Based on the 7 mer DOT1L peptide, a class of peptidomimetics was designed. Compound 21 with modified middle residues, achieved significantly improved binding affinities to AF9 and ENL, with K-D values of 15 nM and 57 nM, respectively. Importantly, 21 recognizes and binds to the cellular AF9 protein and effectively inhibits the AF9-DOT1L interactions in cells. Modifications of the N- and C-termini of 21 resulted in 28 with 2-fold improved binding affinity to AF9 and much decreased peptidic characteristics. Our study provides a proof-of-concept for development of nonpeptidic compounds to inhibit DOT1L activity by targeting its recruitment and the interactions between DOT1L and MLL-oncofusion proteins AF9 and ENL.