endomorphin-1

• 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: endomorphin-1
• 英文别名: H-DL-Tyr-DL-Pro-DL-Trp-DL-Phe-NH2；1-[2-amino-3-(4-hydroxyphenyl)propanoyl]-N-[1-[(1-amino-1-oxo-3-phenylpropan-2-yl)amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
• 化学式: C₃₄H₃₈N₆O₅
• 分子量: 610.713
• InChiKey: ZEXLJFNSKAHNFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  184
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  endomorphin-1 、 N-(fluorenylmethyloxycarbonyl)-L-leucinal 、 (9H-芴-9-基)-2-氧代乙基氨基甲酸甲酯 、 Fmoc-Met-H 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以73%的产率得到
  参考文献：
  名称：

  Synthesis, biological activity and structure–activity relationship of endomorphin-1/substance P derivatives

  摘要：

  Endomorphins have been shown to produce potent analgesia in various rodent models of pain. However, their central administration led to the development of tolerance and physical dependence. Conjugation of C-terminal substance P (SP) fragments to opioids and opioid peptides was previously shown to produce hybrid peptides with strong analgesic activity, with low or no propensity to develop tolerance. In this study, four peptides (2-5) comprised of endomorphin-1 (1) and C-terminal fragments of SP (four or five amino acids, SP8-11 (2) or SP7-11 (4), respectively), with an overlapping Phe residue, were synthesized. To overcome low metabolic stability and poor membrane permeability of the peptide, the N-terminus of 2 and 4 was further modified with a C10-carbon lipoamino acid (C10LAA) achieving 3 and 5, respectively. LAA-modification of the hybrid peptides resulted in a significant increase in metabolic stability and membrane permeability compared to peptides 1,2 and 4. Compound 5 showed potent mu-opioid receptor binding affinity (K-i mu = 3.87 +/- 0.51 nM) with dose-dependent agonist activity in the nanomolar range (IC50 = 45 +/- 13 nM). In silico modeling was used to investigate the binding modes and affinities of compounds 1-5 in the active site of mu-opioid receptors. The docking scores were in agreement with the K-i mu values obtained in the receptor binding affinity studies. The more active LAA-modified hybrid peptide showed a lower total interaction energy and higher negative value of MolDock score. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.003

文献信息

• BIOLOGICAL NANOPORES HAVING TUNABLE PORE DIAMETERS AND USES THEREOF AS ANALYTICAL TOOLS
  申请人：RIJKSUNIVERSITEIT GRONINGEN

  公开号：EP3850001A1

  公开（公告）日：2021-07-21
• [EN] BIOLOGICAL NANOPORES HAVING TUNABLE PORE DIAMETERS AND USES THEREOF AS ANALYTICAL TOOLS<br/>[FR] NANOPORES BIOLOGIQUES AYANT DES DIAMÈTRES DE PORES RÉGLABLES ET LEURS UTILISATIONS EN TANT QU'OUTILS ANALYTIQUES
  申请人：UNIV GRONINGEN

  公开号：WO2020055246A1

  公开（公告）日：2020-03-19

  The invention relates to the field of nanopores, in particular to engineered Fragaceatoxin C (FraC) nanopores and their application in analyzing biopolymers and other (biological) compounds, such as single-molecule (protein) sequencing. Provided is a system comprising oligomeric FraC nanopores comprised in a lipid bilayer, wherein the sum of the nanopore fraction in the heptameric (Type II) state and the nanopore fraction in the hexameric (Type III) state represents at least 60% of the total number of FraC nanopores.