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

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.

Novel highly potent μ-opioid receptor antagonist based on endomorphin-2 structure

The μ-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) exhibit an extremely high selectivity for the μ-opioid receptor and thus represent a potential framework for modification into μ-antagonists. Here we report on the synthesis and biological evaluation of novel [d-2-Nal4]endomorphin-2 analogs, [Sar2,d-2-Nal4]endomorphin-2 and [Dmt1,Sar2,d-2-Nal4]endomorphin-2 (Dmt = 2′6′-dimethyltyrosine; Sar = N-methylglycine, sarcosine; d-2-Nal = 3-(2-naphthyl)-d-alanine). [Dmt1,Sar2,d-2-Nal4]endomorphin-2 possessed very high affinity for the μ-opioid receptor (IC50 = 0.01 ± 0.001 nM) and turned out to be a potent and extremely selective μ-opioid receptor antagonist, as judged by the in vitro aequorin luminescence-based calcium assay (pA2 = 9.19). However, in the in vivo hot plate test in mice this analog was less potent than our earlier μ-opioid receptor antagonist, [Dmt1,d-2-Nal4]endomorphin-2 (antanal-2). The exceptional μ-opioid receptor in vitro activity and selectivity of [Dmt1, Sar2,d-2-Nal4]endomorphin-2 makes this analog a valuable pharmacological tool, but further modifications are needed to improve its in vivo profile.

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.