N-Acetyl-L-leucyl-L-proline | 61434-53-5

• 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: N-Acetyl-L-leucyl-L-proline
• 英文别名: (2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]pyrrolidine-2-carboxylic acid
• CAS: 61434-53-5
• 化学式: C₁₃H₂₂N₂O₄
• 分子量: 270.329
• InChiKey: ZXQDYBJTDFUFSJ-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Acetyl-L-leucyl-L-proline 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.8b00175
• 作为产物：
  描述：

  亮氨酰脯氨酸苄酯 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-Acetyl-L-leucyl-L-proline
  参考文献：
  名称：

  Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.8b00175

文献信息

• Elastase inhibitor
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0639585A1

  公开（公告）日：1995-02-22

  A compound of general formula [I]: or its hydrates wherein R represents hydrogen atom, a lower alkanoyl amino group, a lower alkyloxy carbonylamino group or an aralkyloxy carbonylamino group, R¹ and R² may be identical or different from each other and each represents a lower alkyl group, and R³ represents a C₃-C₆ lower alkyl group, a cycloalkyl lower alkyl group or an aryl lower alkyl group. The compound is effective as an elastase inhibitor and a therapeutic agent.

  通式[I]的化合物或其水合物，其中R代表氢原子、较低的烷酰氨基、较低的烷氧羰基氨基或芳基氧羰基氨基，R¹和R²可以相同也可以不同，每个代表较低的烷基，R³代表C₃-C₆较低的烷基、环烷基较低的烷基或芳基较低的烷基。该化合物作为弹性酶抑制剂和治疗剂具有有效性。
• 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.