3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxycarbonylamino}-propionic acid ethyl ester | 469887-98-7

• 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: 3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxycarbonylamino}-propionic acid ethyl ester
• 英文别名: Ethyl 3-[2-[2-(2-methoxyethoxy)ethoxy]ethoxycarbonylamino]propanoate
• CAS: 469887-98-7
• 化学式: C₁₃H₂₅NO₇
• 分子量: 307.344
• InChiKey: VFTYKPSDTVVOIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxycarbonylamino}-propionic acid ethyl ester 在 肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以100%的产率得到3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxycarbonylamino}-propionyl hydrazide
  参考文献：
  名称：

  Monoclonal Antibody Conjugates of Doxorubicin Prepared with Branched Peptide Linkers:  Inhibition of Aggregation by Methoxytriethyleneglycol Chains

  摘要：

  High mole ratio BR96 immunoconjugates were synthesized using branched peptide-doxorubicin linkers designed to liberate doxorubicin following antigen-specific internalization into lysosomes. However, these immunoconjugates are highly prone to noncovalent, dimeric aggregation. We hypothesize that this is due to (1) the hydrophobic nature of the peptides, (2) the loss of positive charge upon amide formation At the 3'-amino group of doxorubicin, and (3) the proximity of the peptide hydrophobic residues to form efficient intermolecular stacking interactions. By introducing a hydrophilic methoxytriethylene glycol chain onto the doxorubicin portion of the branched peptide linkers, aggregation has been eliminated or greatly reduced in the immunoconjugate products. The methoxytriethylene glycol chain was linked to the doxorubicin moiety of the linker via a hydrazone bond that is stable at pH 7 but hydrolyzes rapidly at pH 5 to release free drug. BR96 immunoconjugates synthesized from methoxytriethylene glycol-modified branched peptide-doxorubicin linkers are highly potent and immunospecific in vitro. The data suggest that the methoxytriethylene glycol chain hydrolyzes as designed upon antigen-specific internalization into tumor lysosomes in vitro, where enzymatic degradation of the peptide linker releases free doxorubicin.

  DOI：

  10.1021/jm020149g
• 作为产物：
  描述：

  三甘醇单甲醚 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 21.5h， 生成 3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxycarbonylamino}-propionic acid ethyl ester
  参考文献：
  名称：

  Monoclonal Antibody Conjugates of Doxorubicin Prepared with Branched Peptide Linkers:  Inhibition of Aggregation by Methoxytriethyleneglycol Chains

  摘要：

  High mole ratio BR96 immunoconjugates were synthesized using branched peptide-doxorubicin linkers designed to liberate doxorubicin following antigen-specific internalization into lysosomes. However, these immunoconjugates are highly prone to noncovalent, dimeric aggregation. We hypothesize that this is due to (1) the hydrophobic nature of the peptides, (2) the loss of positive charge upon amide formation At the 3'-amino group of doxorubicin, and (3) the proximity of the peptide hydrophobic residues to form efficient intermolecular stacking interactions. By introducing a hydrophilic methoxytriethylene glycol chain onto the doxorubicin portion of the branched peptide linkers, aggregation has been eliminated or greatly reduced in the immunoconjugate products. The methoxytriethylene glycol chain was linked to the doxorubicin moiety of the linker via a hydrazone bond that is stable at pH 7 but hydrolyzes rapidly at pH 5 to release free drug. BR96 immunoconjugates synthesized from methoxytriethylene glycol-modified branched peptide-doxorubicin linkers are highly potent and immunospecific in vitro. The data suggest that the methoxytriethylene glycol chain hydrolyzes as designed upon antigen-specific internalization into tumor lysosomes in vitro, where enzymatic degradation of the peptide linker releases free doxorubicin.

  DOI：

  10.1021/jm020149g

文献信息

• Monoclonal Antibody Conjugates of Doxorubicin Prepared with Branched Peptide Linkers:  Inhibition of Aggregation by Methoxytriethyleneglycol Chains
  作者：H. Dalton King、Gene M. Dubowchik、Harold Mastalerz、David Willner、Sandra J. Hofstead、Raymond A. Firestone、Shirley J. Lasch、Pamela A. Trail

  DOI：10.1021/jm020149g

  日期：2002.9.1

  High mole ratio BR96 immunoconjugates were synthesized using branched peptide-doxorubicin linkers designed to liberate doxorubicin following antigen-specific internalization into lysosomes. However, these immunoconjugates are highly prone to noncovalent, dimeric aggregation. We hypothesize that this is due to (1) the hydrophobic nature of the peptides, (2) the loss of positive charge upon amide formation At the 3'-amino group of doxorubicin, and (3) the proximity of the peptide hydrophobic residues to form efficient intermolecular stacking interactions. By introducing a hydrophilic methoxytriethylene glycol chain onto the doxorubicin portion of the branched peptide linkers, aggregation has been eliminated or greatly reduced in the immunoconjugate products. The methoxytriethylene glycol chain was linked to the doxorubicin moiety of the linker via a hydrazone bond that is stable at pH 7 but hydrolyzes rapidly at pH 5 to release free drug. BR96 immunoconjugates synthesized from methoxytriethylene glycol-modified branched peptide-doxorubicin linkers are highly potent and immunospecific in vitro. The data suggest that the methoxytriethylene glycol chain hydrolyzes as designed upon antigen-specific internalization into tumor lysosomes in vitro, where enzymatic degradation of the peptide linker releases free doxorubicin.