141801-26-5

Basic information

• Product Name: ENDOMORPHIN-2
• Synonyms: ENDOMORPHIN-2;ENDOMORPHIN-2 (HUMAN, BOVINE);H-TYR-PRO-PHE-PHE-NH2;YPFF-NH2;TYR-PRO-PHE-PHE-NH2;(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-N-[(1S)-1-[[(1S)-1-carbamoyl-2-phenyl-ethyl]carbamoyl]-2-phenyl-ethyl]pyrrolidine-2-carboxamide;L-Tyrosyl-L-prolyl-L-phenylalanyl-L-phenylalaninamide;L-Phenylalaninamide,L-tyrosyl-L-prolyl-L-phenylalanyl-
• CAS NO: 141801-26-5
• Molecular Formula: C₃₂H₃₇N₅O₅
• Molecular Weight: 571.67
• Product Categories: Peptide;Neuropeptides;Opioid Peptides;Other Opioid Peptides;Other Opioid PeptidesPeptides for Cell Biology;Opioid receptor and opioid-like receptor
• Mol File: 141801-26-5.mol
• Article Data: 6

Chemical Properties

• Melting Point: 130-131℃
• Boiling Point: 972.4°Cat760mmHg
• Flash Point: 541.9°C
• Appearance: White to off-white/Solid
• Density: 1.292g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.632
• Storage Temp.: −20°C
• PKA: 9.86±0.15(Predicted)
• CAS DataBase Reference: ENDOMORPHIN-2(CAS DataBase Reference)
• NIST Chemistry Reference: ENDOMORPHIN-2(141801-26-5)
• EPA Substance Registry System: ENDOMORPHIN-2(141801-26-5)

Safety Data

• WGK Germany: 3
• RTECS: SQ7316100
• Hazardous Substances Data: 141801-26-5(Hazardous Substances Data)

Usage

Uses

Endomorphin-2 is a potent and selective endogenous agonist for the μ-opiate receptor.

InChI:InChI=1/C32H37N5O5/c33-25(18-23-13-15-24(38)16-14-23)32(42)37-17-7-12-28(37)31(41)36-27(20-22-10-5-2-6-11-22)30(40)35-26(29(34)39)19-21-8-3-1-4-9-21/h1-6,8-11,13-16,25-28,38H,7,12,17-20,33H2,(H2,34,39)(H,35,40)(H,36,41)/t25-,26-,27-,28-/m0/s1

Upstream product

• 141801-21-0 Boc-Tyr-Pro-Phe-Phe-NH₂ 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 3978-80-1 Boc-Tyr-OH 
• 907198-94-1 Z-Tyr-Pro-Phe-Phe-NH₂ 
• 71989-31-6 Fmoc-Pro-OH 
• 35661-40-6 N-Fmoc L-Phe 
• 33900-18-4 Cam-3508 
• 65864-22-4 (S)-2-amino-3-phenylpropionamide hydrochloride 
• 40298-71-3 N-tert-butoxycarbonyl-O-2,6-dichlorobenzyl-L-tyrosine 
• 112883-29-1 N-Fmoc-Tyr-OH 
• 73504-61-7 diphenylalaninamide hydrochloride 

Relevant articles and documents

Differential receptor binding characteristics of consecutive phenylalanines in μ-opioid specific peptide ligand endomorphin-2

Endogenous opioid peptides consist of a conserved amino acid residue of Phe3 and Phe4, although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the μ opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe3 and Phe4 in binding to the μ receptor, we synthesized a series of analogs in which Phe3 and Phe4 were replaced by various amino acids. It was found that the aromaticity of the Phe-β-phenyl groups of Phe3 and Phe4 is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe3 and Phe4 of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp3]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses.

Structure-activity study of endomorphin-2 analogs with C-terminal modifications by NMR spectroscopy and molecular modeling

Endomorphin-2 (EM-2) is a putative endogenous μ-opioid receptor ligand. To get insight into the important role of C-terminal amide group of EM-2, we investigated herein a series of EM-2 analogs by substitution of the C-terminal amide group with -NHNH2, -NHCH3, -N(CH3)2, -OCH3, -OCH2CH3, -OC(CH3)3, and -CH2-OH. Their binding affinity and bioactivity were determined and compared. Despite similar (analogs 1, 4, and 7) or decreased (analogs 2, 3,5, and 6) μ affinity in binding assays, all analogs showed low guinea pig ileum (GPI) and mouse vas deferens (MVD) potencies compared to their parent peptide. Interestingly, as for analogs 2 and 3 (a single and double N-methylation of C-terminal amide), the potency order with the Ki (μ) values was 2 > 3; for the C-terminal esterified analogs 4-6, the potency order with the Ki (μ) values was 4 > 5 > 6. Thus, we concluded that the steric hindrance of C-terminus might play an important role in opioid receptor affinity. We further investigated the conformational properties of these analogs by 1D and 2D 1H NMR spectroscopy and molecular modeling. Evaluating the ratios of cis- and trans-isomers, aromatic interactions, dihedral angles, and stereoscopic views of the most convergent conformers, we found that modifications at the C-terminal amide group of EM-2 affected these analog conformations markedly, therefore changed the opioid receptor affinity and in vitro bioactivity.

Structure-Activity Study on the Phe Side Chain Arrangement of Endomorphins Using Conformationally Constrained Analogues

Structure-activity study on the Phe side chain arrangement of endomorphins using conformationally constrained analogues.Endomorphins-1 and -2 were substituted with all the beta-MePhe stereoisomers in their Phe residues to generate a conformationally constrained peptide set. This series of molecules was subjected to biological assays, and for beta-MePhe(4)-endomorphins-2, a conformational analysis was performed. Incorporation of (2S,3S)-beta-MePhe(4) resulted in the most potent analogues of both endomorphins with enhanced enzymatic stability. Their micro opioid affinities were 4-times higher than the parent peptides, they stimulated [(35)S]GTPgammaS binding, and they were found to be full agonists. NMR experiments revealed that C-terminal (2S,3S)-beta-MePhe in endomorphin-2 strongly favored the gauche (-) spatial orientation which implies the presence of the chi(1) = -60 degrees rotamer of Phe(4) in the binding conformer of endomorphins. Our results emphasize that the appropriate orientation of the C-terminal aromatic side chain of endomorphins is substantial for binding to the micro opioid receptor.