(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S,3R)-2-[6-[3-[3-[3,4-dimethoxy-5-[[(2S)-1-prop-2-enylpyrrolidin-2-yl]methylcarbamoyl]phenyl]propylsulfanyl]-2,5-dioxopyrrolidin-1-yl]hexanoylamino]-3-hydroxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carboxylic acid | 1609258-27-6

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: (2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S,3R)-2-[6-[3-[3-[3,4-dimethoxy-5-[[(2S)-1-prop-2-enylpyrrolidin-2-yl]methylcarbamoyl]phenyl]propylsulfanyl]-2,5-dioxopyrrolidin-1-yl]hexanoylamino]-3-hydroxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 1609258-27-6
• 化学式: C₁₀₁H₁₄₀N₂₂O₂₁S₂
• 分子量: 2062.49
• InChiKey: IXSUYJGJHMRPNB-LZPMYQHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  146
• 可旋转键数：
  55
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  653
• 氢给体数：
  18
• 氢受体数：
  26

反应信息

• 作为产物：
  描述：

  3-(3-((1-allylpyrrolidin-2-yl)methylcarbamoyl)-4,5-dimethoxyphenyl)propylthiol 、 以 aq. phosphate buffer 、 乙腈 为溶剂， 反应 0.17h， 以62%的产率得到(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S,3R)-2-[6-[3-[3-[3,4-dimethoxy-5-[[(2S)-1-prop-2-enylpyrrolidin-2-yl]methylcarbamoyl]phenyl]propylsulfanyl]-2,5-dioxopyrrolidin-1-yl]hexanoylamino]-3-hydroxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Shuttle–Cargo Fusion Molecules of Transport Peptides and the hD_2/3Receptor Antagonist Fallypride: A Feasible Approach To Preserve Ligand–Receptor Binding?

  摘要：

  To determine if the conjugation of a small receptor ligand to a peptidic carrier to potentially facilitate transport across the blood brain barrier (BBB) by "molecular Trojan horse" transcytosis is feasible, we synthesized several transport peptide fallypride fusion molecules as model systems and determined their binding affinities to the hD(2) receptor. Although they were affected by conjugation, the binding affinities were found to be still in the nanomolar range (between 1.5 and 64.2 nM). In addition, homology modeling of the receptor and docking studies for the most potent compounds were performed, elucidating the binding modes of the fusion molecules and the structure elements contributing to the observed high receptor binding. Furthermore, no interaction between the hybrid compounds and P-gp, the main excretory transporter of the BBB, was found. From these results, it can be inferred that the approach to deliver small neuroreceptor ligands across the BBB by transport peptide carriers is feasible.

  DOI：

  10.1021/jm5004123

文献信息

• Shuttle–Cargo Fusion Molecules of Transport Peptides and the hD_2/3Receptor Antagonist Fallypride: A Feasible Approach To Preserve Ligand–Receptor Binding?
  作者：Carmen Wängler、Shafinaz Chowdhury、Georg Höfner、Petia Djurova、Enrico O. Purisima、Peter Bartenstein、Björn Wängler、Gert Fricker、Klaus T. Wanner、Ralf Schirrmacher

  DOI：10.1021/jm5004123

  日期：2014.5.22

  To determine if the conjugation of a small receptor ligand to a peptidic carrier to potentially facilitate transport across the blood brain barrier (BBB) by "molecular Trojan horse" transcytosis is feasible, we synthesized several transport peptide fallypride fusion molecules as model systems and determined their binding affinities to the hD(2) receptor. Although they were affected by conjugation, the binding affinities were found to be still in the nanomolar range (between 1.5 and 64.2 nM). In addition, homology modeling of the receptor and docking studies for the most potent compounds were performed, elucidating the binding modes of the fusion molecules and the structure elements contributing to the observed high receptor binding. Furthermore, no interaction between the hybrid compounds and P-gp, the main excretory transporter of the BBB, was found. From these results, it can be inferred that the approach to deliver small neuroreceptor ligands across the BBB by transport peptide carriers is feasible.