864084-88-8

Basic information

• Product Name: OPIORPHIN
• Synonyms: OPIORPHIN;H-Gln-Arg-Phe-Ser-Arg-OH;L-Arginine,L-glutaminyl-L-arginyl-L-phenylalanyl-L-seryl-;L-Glutaminyl-L-arginyl-L-phenylalanyl-L-seryl-L-arginine
• CAS NO: 864084-88-8
• Molecular Formula: C₂₉H₄₈N₁₂O₈
• Molecular Weight: 692.774
• Mol File: 864084-88-8.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Storage Temp.: ?20°C
• CAS DataBase Reference: OPIORPHIN(CAS DataBase Reference)
• NIST Chemistry Reference: OPIORPHIN(864084-88-8)
• EPA Substance Registry System: OPIORPHIN(864084-88-8)

Safety Data

• Hazardous Substances Data: 864084-88-8(Hazardous Substances Data)

Usage

General Description

Opiorphin is a natural peptide derived from hemoglobin that acts as a potent painkiller. It works by inhibiting the enzyme neutral endopeptidase, which breaks down endorphins, the body's natural pain-relieving compounds. Opiorphin is able to enhance the body's own pain inhibition system, leading to an increase in pain relief without the risk of addiction or dependence. Studies have shown that opiorthin is as effective as morphine in relieving pain, but without the unwanted side effects such as tolerance and respiratory depression. As a result, opiorthin has the potential to be developed as a new and improved pain management medication.

Synthetic route

Fmoc-Arg(Pbf)-Wang resin + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-L-Gln(Trt)-OH (132327-80-1) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → human opiorphin (864084-88-8)

Conditions	Yield
Stage #1: Fmoc-Arg(Pbf)-Wang resin With piperidine In N,N-dimethyl-formamide solid phase reaction; Stage #2: Fmoc-Ser(tBu)-OH With benzotriazol-1-ol; diisopropyl-carbodiimide In N,N-dimethyl-formamide for 2h; solid phase reaction; Stage #3: N-Fmoc L-Phe; Fmoc-L-Gln(Trt)-OH; Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine Further stages;

N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-L-Gln(Trt)-OH (132327-80-1) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → human opiorphin (864084-88-8)

Conditions

Yield

Stage #1: Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine With N-ethyl-N,N-diisopropylamine In dichloromethane solid phase reaction; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.166667h; solid phase reaction; Stage #3: N-Fmoc L-Phe; Fmoc-Ser(tBu)-OH; Fmoc-L-Gln(Trt)-OH; Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine Further stages;

23.4 mg

Fmoc-Arg(Pmc)-WANG resin + N-Fmoc L-Phe (35661-40-6) + Fmoc-L-Gln(Trt)-OH (132327-80-1) + Fmoc-L-Arg-OH (91000-69-0) + Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether (71989-33-8, 128107-47-1) → human opiorphin (864084-88-8)

Conditions	Yield
Stage #1: Fmoc-Arg(Pmc)-WANG resin With piperidine In N,N-dimethyl-formamide solid phase reaction; Stage #2: Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether With benzotriazol-1-ol; diisopropyl-carbodiimide In N,N-dimethyl-formamide Stage #3: N-Fmoc L-Phe; Fmoc-L-Gln(Trt)-OH; Fmoc-L-Arg-OH Further stages;

Fmoc-Arg(Pmc)-WANG resin + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-L-Gln(Trt)-OH (132327-80-1) + Fmoc-Arg(Pbf)-OH (119831-72-0) → human opiorphin (864084-88-8)

Conditions	Yield
Stage #1: Fmoc-Arg(Pmc)-WANG resin With piperidine In N,N-dimethyl-formamide WANG resin; Stage #2: Fmoc-Ser(tBu)-OH With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide WANG resin; Stage #3: N-Fmoc L-Phe; Fmoc-L-Gln(Trt)-OH; Fmoc-Arg(Pbf)-OH Further stages;

Upstream product

• 35661-40-6 N-Fmoc L-Phe 
• 71989-33-8 Fmoc-Ser(tBu)-OH 
• 132327-80-1 Fmoc-L-Gln(Trt)-OH 
• 187618-60-6 Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine 
• 119831-72-0 Fmoc-Arg(Pbf)-OH 
• 91000-69-0 Fmoc-L-Arg-OH 
• 71989-33-8 Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether 

Relevant articles and documents

Structure-activity relationship study of opiorphin, a human dual ectopeptidase inhibitor with antinociceptive properties

Toward developing new potential analgesics, this first structure-activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe3 is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalinase inhibition. A series of Phe3-halogenated analogues revealed that halogen bonding based optimization strategies are not applicable to this residue. Additional substituted Phe3 derivatives showed that replacing l-Phe3 for d-Phe3 increased the AP-N inhibition potency by 1 order of magnitude. NMR studies and molecular mechanics calculations indicated that the improved potency may be due to CH-π stacking interactions between the aromatic ring of d-Phe3 and the Hγ protons of Arg2. This structural motif is not possible for the native opiorphin and may be useful for the design of further potent and metabolically stable analogues.

Influence of polar side chains modifications on the dual enkephalinase inhibitory activity and conformation of human opiorphin, a pain perception related peptide

The dual inhibitory action of the pain related peptide opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH) against neutral endopeptidase (NEP) and aminopeptidase N (AP-N) was further investigated by a SAR study involving minor modifications on the polar side chains of Arg residues and glycosylation with monosaccharides at Ser. None of them exerted dual or individual inhibitory potency superior than opiorphin. However, the correlations deduced offer further proof for the key role of these residues upon the binding and bioactive conformational stabilization of opiorphin. NMR conformational studies on the glycopeptides suggest that they are still very flexible compounds that may attain their respective bioactive conformations.