{(1S,2S)-1-[(S)-1-(Carbamoylmethyl-carbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester | 175444-61-8

• 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: {(1S,2S)-1-[(S)-1-(Carbamoylmethyl-carbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester
• CAS: 175444-61-8
• 化学式: C₁₉H₃₆N₄O₅
• 分子量: 400.519
• InChiKey: CDTSGNNJLIJSIC-YDHLFZDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.06
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  139.62
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  {(1S,2S)-1-[(S)-1-(Carbamoylmethyl-carbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester 在 sodium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 benzyl (2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-benzyl-3-[[[(2S)-4-methyl-2-[[(2S,3S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]pentanoyl]amino]methylamino]-3-oxopropanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylmethoxybutanoyl]amino]-4-methylpentanoate
  参考文献：
  名称：

  Partially Modified Retro-Inverso Pseudopeptides as Non-natural Ligands for the Human Class I Histocompatibility Molecule HLA-A2

  摘要：

  Syntheses of a series of partially modified retro-inverso analogues of the antigenic peptide M58-66 derived from the influenza virus matrix protein are reported. The retro-inverso modification Psi(NH-CO) was obtained by replacement of two successive amino acid residues with a 2-substituted malonate derivative and gem-diaminoalkyl residue. The resulting compounds 1-8 were tested for their binding to the human histocompatibility class I molecule HLA-A2 in an assembly assay using lysates of peptide transporter-deficient cells T2. Specific peptide-dependent HLA-A2 assembly was revealed by an enzyme-linked immunosorbent assay. Significant HLA-A2 assembly was detected in the presence of analogues [gGly(58)-(S)mLeu(59)]-M58-66 (1a), [gGly(61)-(R,S)mPhe(62)]M58-66 (4), [gVal(63)-(R,S)mPhe(64)]M58-66 (6), and [gPhe(64)-(R,S)mAla(65)]M58-66 (7). The introduction of the retro-inverso modification between P2-P3, P3-P4, P5-P6, and P8-P9 (compounds 2, 3, 5, and 8, respectively) however led to a dramatic reduction in peptide binding to HLA-A2. Interestingly, compound 1a which contains modification between P1-P2 was found to be the most potent analogue, being able to retain the original HLA-A2 binding profile of the parent peptide M58-66. Taken together, these results and recent binding data obtained in the context of murine MHC class I molecule H-2K(d) suggest that the incorporation of peptide bond surrogates in MHC class I-restricted epitopes is a useful approach to design molecules having both increased stability and high MHC-binding capacity. Depending on their agonist or antagonist effects at the T-cell receptor, such non-natural MHC ligands are likely to find many applications in the development of peptide-based vaccines or as potential therapeutic agents in the treatment of allergies and autoimmune diseases.

  DOI：

  10.1021/jm9509511
• 作为产物：
  描述：

  BOC-L-异亮氨酸 、 leucyl-glycine amide trifluoroacetate 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以50%的产率得到{(1S,2S)-1-[(S)-1-(Carbamoylmethyl-carbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-butyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Partially Modified Retro-Inverso Pseudopeptides as Non-natural Ligands for the Human Class I Histocompatibility Molecule HLA-A2

  摘要：

  Syntheses of a series of partially modified retro-inverso analogues of the antigenic peptide M58-66 derived from the influenza virus matrix protein are reported. The retro-inverso modification Psi(NH-CO) was obtained by replacement of two successive amino acid residues with a 2-substituted malonate derivative and gem-diaminoalkyl residue. The resulting compounds 1-8 were tested for their binding to the human histocompatibility class I molecule HLA-A2 in an assembly assay using lysates of peptide transporter-deficient cells T2. Specific peptide-dependent HLA-A2 assembly was revealed by an enzyme-linked immunosorbent assay. Significant HLA-A2 assembly was detected in the presence of analogues [gGly(58)-(S)mLeu(59)]-M58-66 (1a), [gGly(61)-(R,S)mPhe(62)]M58-66 (4), [gVal(63)-(R,S)mPhe(64)]M58-66 (6), and [gPhe(64)-(R,S)mAla(65)]M58-66 (7). The introduction of the retro-inverso modification between P2-P3, P3-P4, P5-P6, and P8-P9 (compounds 2, 3, 5, and 8, respectively) however led to a dramatic reduction in peptide binding to HLA-A2. Interestingly, compound 1a which contains modification between P1-P2 was found to be the most potent analogue, being able to retain the original HLA-A2 binding profile of the parent peptide M58-66. Taken together, these results and recent binding data obtained in the context of murine MHC class I molecule H-2K(d) suggest that the incorporation of peptide bond surrogates in MHC class I-restricted epitopes is a useful approach to design molecules having both increased stability and high MHC-binding capacity. Depending on their agonist or antagonist effects at the T-cell receptor, such non-natural MHC ligands are likely to find many applications in the development of peptide-based vaccines or as potential therapeutic agents in the treatment of allergies and autoimmune diseases.

  DOI：

  10.1021/jm9509511