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

• 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.
  作者：TAKASHI ABIKO、HIROSHI SEKINO

  DOI：10.1248/cpb.32.228

  日期：——

  Six common amino acid sequence fragments of thymosins β4, β8 and β9, H-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-OH (positions 16-26), H-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-OH (positions 31-39), H-Asp-Lys-Pro-Asp-OH (positions 2-5), H-Phe-Asp-Lys-OH (positions 12-14), H-Leu-Pro-OH (positions 28-29) and H-Glu-Ile-OH (positions 8-9), were synthesized by the solution method, and were tested to determine their effects on the low E-rosette forming cells of lupus nephritis patients. Two of the fragments, H-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-OH and H-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-OH, increased E-rosette forming capacity when incubated in vitro with patient's blood though they were less effective than thymosin β9, but the other four peptide fragments, H-Asp-Lys-Pro-Asp-OH, H-Phe-Asp-Lys-OH, H-Leu-Pro-OH and H-Glu-Ile-OH, had no effect.

  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。
• 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.