PRSFLVRKP

• 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: PRSFLVRKP
• 英文别名: H-Pro-Arg-Ser-Phe-Leu-Val-Arg-Lys-Pro-NH2；(2S)-1-[(2S)-6-amino-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-pyrrolidine-2-carbonyl]amino]pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]pentanoyl]amino]hexanoyl]pyrrolidine-2-carboxamide
• 化学式: C₅₁H₈₇N₁₇O₁₀
• 分子量: 1098.36
• InChiKey: ZXCSIVUQPNAIJY-LCQMPJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  78
• 可旋转键数：
  34
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  454
• 氢给体数：
  15
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-Lys(Dde)-OH 、 Fmoc-Pbf-L-精氨酸 在 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 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 生成 PRSFLVRKP
  参考文献：
  名称：

  Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker

  摘要：

  We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" disulfide-based linkage that would be cleaved and completely removed in a reducing environment, regenerating the original linear peptide without any linker-related structure. Thus, the linker would serve as a redox switch that would be activated in the intracellular environment. We applied this strategy to a lysine-specific demethylase 1 (LSD1) inhibitor peptide 1. The resulting cyclic peptide 2 exhibited approximately 20 times weaker LSD1-inhibitory activity than peptide 1. Upon addition of reducing reagent, the linker was completely removed to regenerate the linear peptide 1, with full restoration of the LSD1-inhibitory activity. In addition, the cyclic peptide was far less susceptible to proteolysis than the linear counterpart. Thus, this switch design not only enables control of functional activity, but also improves stability. This approach should be applicable to a wide range of peptides, and may be useful in the development of peptide pharmaceuticals. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.12.033

文献信息

• Structure-Based Identification of Potent Lysine-Specific Demethylase 1 Inhibitor Peptides and Temporary Cyclization to Enhance Proteolytic Stability and Cell Growth-Inhibitory Activity
  作者：Hiroki Kitagawa、Masaki Kikuchi、Shin Sato、Hisami Watanabe、Naoki Umezawa、Maiko Kato、Yosuke Hisamatsu、Takashi Umehara、Tsunehiko Higuchi

  DOI：10.1021/acs.jmedchem.0c01371

  日期：2021.4.8

  to a redox-activatable cyclic peptide incorporating cell-penetrating peptide (CPP), expecting selective activation under intracellular reducing conditions. The cyclic peptide moiety exhibited enhanced stability to protease and was converted to the linear, unmodified LSD1 inhibitor peptide under reducing conditions. The cyclic peptide with CPP inhibited the proliferation of human acute myeloid leukemia

  肽是有吸引力的候选药物，但是其用途受到蛋白水解降解的固有敏感性以及无法通过细胞膜的极大限制。在这里，我们采用暂时环化的策略来开发细胞活性的赖氨酸特异性脱甲基酶1（LSD1 / KDM1A）抑制剂肽。我们首先在结合抑制剂肽的LSD1·CoREST的X射线晶体结构数据的帮助下，鉴定了一种高效的LSD1抑制性线性肽。将该肽转化为掺入细胞穿透肽（CPP）的可氧化还原激活的环状肽，期望在细胞内还原条件下进行选择性激活。环状肽部分对蛋白酶表现出增强的稳定性，并在还原条件下转化为线性，未修饰的LSD1抑制剂肽。
• Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker
  作者：Yuichi Amano、Naoki Umezawa、Shin Sato、Hisami Watanabe、Takashi Umehara、Tsunehiko Higuchi

  DOI：10.1016/j.bmc.2016.12.033

  日期：2017.2

  We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" disulfide-based linkage that would be cleaved and completely removed in a reducing environment, regenerating the original linear peptide without any linker-related structure. Thus, the linker would serve as a redox switch that would be activated in the intracellular environment. We applied this strategy to a lysine-specific demethylase 1 (LSD1) inhibitor peptide 1. The resulting cyclic peptide 2 exhibited approximately 20 times weaker LSD1-inhibitory activity than peptide 1. Upon addition of reducing reagent, the linker was completely removed to regenerate the linear peptide 1, with full restoration of the LSD1-inhibitory activity. In addition, the cyclic peptide was far less susceptible to proteolysis than the linear counterpart. Thus, this switch design not only enables control of functional activity, but also improves stability. This approach should be applicable to a wide range of peptides, and may be useful in the development of peptide pharmaceuticals. (C) 2016 Elsevier Ltd. All rights reserved.