189388-22-5

Basic information

• Product Name: ENDOMORPHIN-1
• Synonyms: L-Tyrosyl-L-prolyl-L-tryptophyl-L-phenylalaninamide;L-Phenylalaninamide,L-tyrosyl-L-prolyl-L-tryptophyl-;H-TYR-PRO-TRP-PHE-NH2;ENDOMORPHIN-1;ENDOMORPHIN-1 (HUMAN, BOVINE);TYR-PRO-TRP-PHE-NH2;YPWF-NH2;(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-N-[(1S)-1-[[(1S)-1-carbamoyl-2-phenyl-ethyl]carbamoyl]-2-(1H-indol-3-yl)ethyl]pyrrolidine-2-carboxamide
• CAS NO: 189388-22-5
• Molecular Formula: C34H38N6O5
• Molecular Weight: 610.7
• Product Categories: Other Opioid Peptides;Other Opioid PeptidesPeptides for Cell Biology;Opioid receptor and opioid-like receptor;SignalTransduction;Peptide;Neuropeptides;Opioid Peptides
• Mol File: 189388-22-5.mol
• Article Data: 9

Chemical Properties

• Melting Point: 144-146℃
• Boiling Point: 1052.765 °C at 760 mmHg
• Flash Point: 590.491 °C
• Appearance: White to off-white/Solid
• Density: 1.343 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.671
• Storage Temp.: −20°C
• Solubility: ≥14.9 mg/mL in H2O; ≥30.55 mg/mL in DMSO; ≥47 mg/mL in EtOH
• PKA: 9.86±0.15(Predicted)
• CAS DataBase Reference: ENDOMORPHIN-1(CAS DataBase Reference)
• NIST Chemistry Reference: ENDOMORPHIN-1(189388-22-5)
• EPA Substance Registry System: ENDOMORPHIN-1(189388-22-5)

Safety Data

• WGK Germany: 3
• RTECS: SQ7316800
• Hazardous Substances Data: 189388-22-5(Hazardous Substances Data)

Usage

Biological Activity

endomorphins are two endogenous opioid peptides. endomorphin-1 (tyr-pro-trp-phe-nh2) and endomorphin-2 (tyr-pro-phe-phe-nh2) are tetrapeptides with the highest known affinity and specificity for the μ opioid receptor. endomorphin-1 is located in the nucleus of the solitary tract, the periventricular hypothalamus, and the dorsomedial hypothalamus, where it is found within histaminergic neurons and may regulate sedative and arousal behaviors(1). it is assumed that endomorphins are the cleavage products of a larger precursor, but this polypeptide or protein has not yet been identified. perikarya expressing em2-like immunoreactivity were present in the posterior hypothalamus, whereas those expressing em1-like immunoreactivity were present in both the posterior hypothalamus and the nucleus of the solitary tract (nts). em1-like immunoreactivity was more widely and densely distributed throughout the brain than was em2-like immunoreactivity, whereas em2-like immunoreactivity was more prevalent in the spinal cord than was em1-like immunoreactivity. endomorphins participate in modulating nociceptive and autonomic nervous system processes and responsiveness to stress.figure1 formula of endomorphin-1figure 2 the endomorphin system and its evolving neurophysiological role

references

1. Greco, MA; Fuller, PM; Jhou, TC; Martin-Schild, S; Zadina, JE; Hu, Z; Shiromani, P; Lu, J (2008). "Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus". Brain Research 1245: 96–107.

InChI:InChI=1/C34H38N6O5/c35-26(17-22-12-14-24(41)15-13-22)34(45)40-16-6-11-30(40)33(44)39-29(19-23-20-37-27-10-5-4-9-25(23)27)32(43)38-28(31(36)42)18-21-7-2-1-3-8-21/h1-5,7-10,12-15,20,26,28-30,37,41H,6,11,16-19,35H2,(H2,36,42)(H,38,43)(H,39,44)/t26-,28-,29-,30-/m0/s1

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 3978-80-1 Boc-Tyr-OH 
• 13139-14-5 Boc-Trp-OH 
• 40298-71-3 N-tert-butoxycarbonyl-O-2,6-dichlorobenzyl-L-tyrosine 
• 47355-10-2 Nα-tert-butoxycarbonyl-1-formyl-L-tryptophan 
• 51871-47-7 H-Tyr-Pro-OH 
• 74201-47-1 (tert-butoxycarbonyl)-L-tyrosyl-L-proline 
• 158276-61-0 2-amino-N-(1-amino-1-oxo-3-phenylpropan-2-yl)-3-(1H-indol-3-yl)propanamide 
• 82609-80-1 methyl 1-(2-((t-butoxycarbonyl)amino)-3-(4-hydroxyphenyl)propanoyl)pyrrolidine-2-carboxylate 
• 351184-02-6 Boc-Tyr-Pro-Trp-PheNH₂ 
• 65864-22-4 (S)-2-amino-3-phenylpropionamide hydrochloride 
• 37784-17-1 N-(tert-butoxycarbonyl)-D-proline 
• 71989-31-6 Fmoc-Pro-OH 

Relevant articles and documents

Synthesis and biological evaluation of an orally active glycosylated endomorphin-1

The endogenous opioid peptide endomorphin-1 (1) was modified by attachment of lactose to the N-terminus via a succinamic acid spacer to produce compound 2. The carbohydrate modification significantly improved the metabolic stability and membrane permeability of 2 while retaining μ-opioid receptor binding affinity and agonist activity. Analogue 2 produced dose-dependent antinociceptive activity following intravenous administration in a chronic constriction injury (CCI) rat model of neuropathic pain with an ED50 of 8.3 (±0.8) μmol/kg. The corresponding ED50 for morphine was 2.6 (±1.4) ±mol/kg. Importantly, compound 2 produced dose-dependent pain relief after oral administration in CCI rats (ED 50 = 19.6 (±1.2) ±mol/kg), which was comparable with that of morphine (ED50 = 20.7 (±3.6) μmol/kg). Antineuropathic effects of analogue 2 were significantly attenuated by pretreatment of animals with the opioid antagonist naloxone, confirming opioid receptor-mediated analgesia. In contrast to morphine, no significant constipation was produced by compound 2 after oral administration.

Modulation of the Interaction between a Peptide Ligand and a G Protein-Coupled Receptor by Halogen Atoms

Systematic halogenation of two native opioid peptides has shown that halogen atoms can modulate peptide-receptor interactions in different manners. First, halogens may produce a steric hindrance that reduces the binding of the peptide to the receptor. Second, chlorine, bromine, or iodine may improve peptide binding if their positive σ-hole forms a halogen bond interaction with negatively charged atoms of the protein. Lastly, the negative electrostatic potential of fluorine can interact with positively charged atoms of the protein to improve peptide binding.

Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides

Endomorphin 1 (Endo-1 = Tyr-Pro-Trp-Phe-NH2), an endogenous opioid with high affinity and selectivity for μ-opioid receptors, mediates acute and neuropathic pain in rodents. To overcome metabolic instability and poor membrane permeability, the N- and C-termini of Endo-1 were modified by lipoamino acids (Laa) and/or sugars, and 2′,6′-dimethyltyrosine (Dmt) replacement of Tyr. Analogues were assessed for μ-opioid receptor affinity, inhibition of cAMP accumulation, enzymatic stability, and permeability across Caco-2 cell monolayers. C-Terminus modification decreased receptor affinity, while N-terminus C8-Laa improved stability and permeability with slight change in receptor affinity. Dmt provided a promising lead compound: [C8Laa-Dmt[1]]-Endo-1 is nine times more stable (t1/2 = 43.5 min), >8-fold more permeable in Caco-2 cell monolayers, and exhibits 140-fold greater μ-opioid receptor affinity (Kiμ = 0.08 nM).