Boc-Gln-Leu-Pro-Gly-OCho | 155738-80-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: Boc-Gln-Leu-Pro-Gly-OCho
• CAS: 155738-80-0
• 化学式: C₅₀H₈₃N₅O₈
• 分子量: 882.238
• InChiKey: WTDHBRYVLDOACG-BNVIJBOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  63.0
• 可旋转键数：
  18.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  186.23
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  Boc-Gln-Leu-Pro-Gly-OCho 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 51.0h， 生成 Ala-Pro-Gln-Leu-Pro-Gly-OCho
  参考文献：
  名称：

  Metabolism-Based Brain-Targeting System for a Thyrotropin-Releasing Hormone Analogue

  摘要：

  Gln-Leu-Pro-Gly, a progenitor sequence for the thyrotropin-releasing hormone (TRH) analogue [Leu(2)]TRH (pGlu-Leu-Pro-NH2), was covalently and bioreversibly modified on its N- and C-termini (by a 1,4-dihydrotrigonellyl and a cholesteryl group, respectively) to create lipoidal brain-targeting systems for the TRH analogue. The mechanism of targeting and the recovery of the parent peptide at the target site involve several enzymatic steps, including the oxidation of the 1,4-dihydropyridine moiety. Due to the lipid insolublity of the peptide pyridinium conjugate obtained after this reaction, one of the rudimentary steps of brain targeting (i.e., trapping in the central nervous system) can be accomplished. Our design also included spacer amino acid(s) inserted between the N-terminal residue of the progenitor sequence and the dihydrotrigonellyl group to facilitate the posttargeting removal of the attached modification. The release of the TRH analogue in the brain is orchestrated by a sequential metabolism utilizing esterase/lipase, peptidyl glycine alpha-amidating monooxygenase (PAM), peptidase cleavage, and glutaminyl cyclase. In addition to in vitro experiments to prove the designed mechanism of action, the efficacy of brain targeting for [Leu(2)]TRH administered in the form of chemical-targeting systems containing the embedded progenitor sequence was monitored by the antagonistic effect of the peptide on the barbiturate-induced anesthesia (measure of the activational effect on cholinergic neurons) in mice, and considerable improvement was achieved over the efficacy of the parent peptide upon casing this paradigm.

  DOI：

  10.1021/jm980526i
• 作为产物：
  描述：

  Pro-Gly-OCho 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 49.0h， 生成 Boc-Gln-Leu-Pro-Gly-OCho
  参考文献：
  名称：

  Metabolism-Based Brain-Targeting System for a Thyrotropin-Releasing Hormone Analogue

  摘要：

  Gln-Leu-Pro-Gly, a progenitor sequence for the thyrotropin-releasing hormone (TRH) analogue [Leu(2)]TRH (pGlu-Leu-Pro-NH2), was covalently and bioreversibly modified on its N- and C-termini (by a 1,4-dihydrotrigonellyl and a cholesteryl group, respectively) to create lipoidal brain-targeting systems for the TRH analogue. The mechanism of targeting and the recovery of the parent peptide at the target site involve several enzymatic steps, including the oxidation of the 1,4-dihydropyridine moiety. Due to the lipid insolublity of the peptide pyridinium conjugate obtained after this reaction, one of the rudimentary steps of brain targeting (i.e., trapping in the central nervous system) can be accomplished. Our design also included spacer amino acid(s) inserted between the N-terminal residue of the progenitor sequence and the dihydrotrigonellyl group to facilitate the posttargeting removal of the attached modification. The release of the TRH analogue in the brain is orchestrated by a sequential metabolism utilizing esterase/lipase, peptidyl glycine alpha-amidating monooxygenase (PAM), peptidase cleavage, and glutaminyl cyclase. In addition to in vitro experiments to prove the designed mechanism of action, the efficacy of brain targeting for [Leu(2)]TRH administered in the form of chemical-targeting systems containing the embedded progenitor sequence was monitored by the antagonistic effect of the peptide on the barbiturate-induced anesthesia (measure of the activational effect on cholinergic neurons) in mice, and considerable improvement was achieved over the efficacy of the parent peptide upon casing this paradigm.

  DOI：

  10.1021/jm980526i

文献信息

• Synthesis and behavioral evaluation of a chemical brain-targeting system for a thyrotropin-releasing hormone analogue
  作者：Laszlo Prokai、Xudong Ouyang、Katalin Prokai-Tatrai、James W. Simpkins、Nicholas Bodor

  DOI：10.1016/s0223-5234(99)80012-9

  日期：1998.11

  A chemical brain-targeting system, in which a redox 1,4-dihydropyridine <=> pyridinium function serves as a targeting moiety and a cholesteryl ester contributes to the improved penetration across the blood-brain barrier, was synthesized for a centrally active TRH analogue, pGlu-Leu-Pro-NH2. Our retrometabolic design was also based on the progenitor sequence, Gln-Leu-Pro-Gly, where the C-terminal glycine (Gly) functions as an amide precursor via peptidyl glycine alpha-amidating monooxygenase (PAM) and glutamine (Gln) is the precursor of the N-terminal pyroglutamyl (pGlu) by glutaminyl cyclase. The molecular design included an endopeptidase (post-proline cleaving enzyme) cleavable spacer function. Treatment with the chemical targeting system significantly improved memory-related behavior, without altering thyroid function, in a passive avoidance paradigm in rats bearing bilateral fimbrial lesions. (C) Elsevier, Paris.