58569-55-4

Basic information

• Product Name: H-TYR-GLY-GLY-PHE-MET-OH
• Synonyms: porcine,beta-endorphin1-5;[Met5]Enkephalin acetate salt hydrate;methionine enkephalin acetate;N-[N-[N-(N-L-tyrosylglycyl)glycyl]-L-phenylalanyl]-L-methionine;(methionine5)enkephalin;[5-Methionin]Enkephalin, Enkephalin M;[Met5]Enkephalin hydrate acetate salt;TYR-GLY-GLY-PHE-MET H2O
• CAS NO: 58569-55-4
• Molecular Formula: C27H35N5O7S
• Molecular Weight: 573.66
• EINECS: 261-335-8
• Product Categories: Peptide;Opioid receptor and opioid-like receptor;Pepetides;peptides
• Mol File: 58569-55-4.mol

Chemical Properties

• Melting Point: 174-177 °C
• Boiling Point: 1052.9 °C at 760 mmHg
• Flash Point: 590.6 °C
• Appearance: white/powder
• Density: 1.324 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.608
• Storage Temp.: −20°C
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated, Sonicated), Water (Slightly)
• PKA: 3.23±0.10(Predicted)
• Stability: Unstable in alkaline solution
• CAS DataBase Reference: H-TYR-GLY-GLY-PHE-MET-OH(CAS DataBase Reference)
• NIST Chemistry Reference: H-TYR-GLY-GLY-PHE-MET-OH(58569-55-4)
• EPA Substance Registry System: H-TYR-GLY-GLY-PHE-MET-OH(58569-55-4)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• F: 3-10-21
• Hazardous Substances Data: 58569-55-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
H-TYR-GLY-GLY-PHE-MET-OH is used as an analgesic agent for its pain-relieving properties. It can help alleviate moderate to severe pain by binding to the opioid receptors in the central nervous system, reducing the perception of pain.
Used in Cell Proliferation and Differentiation:
Met-enkephalin is used as a growth factor to stimulate cell proliferation and differentiation in various cell types. It can promote tissue repair and regeneration, making it a potential therapeutic agent for wound healing and tissue engineering applications.
Used in Immunomodulation:
H-TYR-GLY-GLY-PHE-MET-OH is used as an immunomodulatory agent for its ability to modulate the immune system. It can influence the activity of immune cells, such as macrophages and lymphocytes, and may have potential applications in treating autoimmune diseases and enhancing immune responses against infections.
Used in Neuroprotection:
Met-enkephalin is used as a neuroprotective agent due to its potential to protect neurons from damage and degeneration. It may have applications in the treatment of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, by reducing neuronal cell death and promoting neuronal survival.
Used in Anticancer Applications:
H-TYR-GLY-GLY-PHE-MET-OH can be used as an anticancer agent, as it may inhibit the growth and proliferation of certain cancer cells. It could potentially be used in combination with conventional chemotherapeutic drugs to enhance their efficacy and overcome drug resistance in cancer treatment.
Used in Drug Delivery Systems:
Met-enkephalin can be incorporated into drug delivery systems to improve the targeting and efficacy of therapeutic agents. By conjugating Met-enkephalin with drug carriers, such as nanoparticles or liposomes, it may enhance the delivery of drugs to specific cells or tissues, improving their therapeutic outcomes.

InChI:InChI=1/C27H35N5O7S/c1-40-12-11-21(27(38)39)32-26(37)22(14-17-5-3-2-4-6-17)31-24(35)16-29-23(34)15-30-25(36)20(28)13-18-7-9-19(33)10-8-18/h2-10,20-22,33H,11-16,28H2,1H3,(H,29,34)(H,30,36)(H,31,35)(H,32,37)(H,38,39)/t20-,21-,22-/m0/s1

Synthetic route

(S)-2-{(S)-2-[2-(2-{(S)-3-[4-(4-Bromo-phenoxycarbonyloxy)-phenyl]-2-tert-butoxycarbonylamino-propionylamino}-acetylamino)-acetylamino]-3-phenyl-propionylamino}-4-methanesulfinyl-butyric acid → met-enkephalin (58569-55-4)

Conditions	Yield
With p-cresol; dimethylsulfide; hydrogen fluoride at 0℃; for 1h;	92%

boc-Tyr-Gly-Gly-Phe-Met-OH (59481-77-5) → met-enkephalin (58569-55-4)

Conditions	Yield
With hydrogenchloride; acetic acid for 1h;	90%
With hydrogenchloride In acetic acid for 0.5h;	85%

Boc-Tyr-Gly-Gly-Phe-Met-OBut (82362-16-1) → met-enkephalin (58569-55-4)

Conditions	Yield
With methyl-phenyl-thioether; trifluoroacetic acid for 1h; Ambient temperature;	74%

C17H13NO10S2(2-)*2Na(1+) + C20H19NO10S3(2-)*2Na(1+) + C24H19NO10S2(2-)*2Na(1+) + C24H19NO11S2(2-)*2Na(1+) → met-enkephalin (58569-55-4)

Conditions	Yield
Stage #1: C20H19NO10S3(2-)*2Na(1+) With sodium hydrogencarbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; ethyl cyanoglyoxylate-2-oxime In water; acetonitrile at 20℃; for 0.75h; Stage #2: With ethanolamine In water for 0.166667h; Stage #3: C17H13NO10S2(2-)*2Na(1+); C24H19NO10S2(2-)*2Na(1+); C24H19NO11S2(2-)*2Na(1+) Further stages;	63%

Boc-Tyr(Mtb)-Gly-Gly-Phe-Met-OMtb (129398-74-9) → met-enkephalin (58569-55-4)

Conditions	Yield
With 3,5-dimethylmethoxybenzene; ethane-1,2-dithiol; trifluoroacetic acid 1) 0 deg C, 120 min, 2) 20 deg C, 60 min;	57%

Boc-Tyr(Cl2Bzl)-Gly-Gly-Phe-Met-OBzl (129398-68-1) → met-enkephalin (58569-55-4)

Conditions	Yield
With trifluorormethanesulfonic acid; methyl-phenyl-thioether; ethane-1,2-dithiol; 3-methyl-phenol; trifluoroacetic acid at 0℃; for 1.5h;	49%

N-(diphenylphosphinoyl)tyrosylglycylglycylphenylalanylmethionine (148715-90-6) → met-enkephalin (58569-55-4)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 6h;	40%

Boc-Tyr(tert.-Bu)-Gly-Gly-Phe-Met (62530-43-2) → met-enkephalin (58569-55-4)

Conditions	Yield
With hydrogenchloride; ethane-1,2-dithiol; methoxybenzene In 1,4-dioxane for 1h; Ambient temperature; Yield given;

Z-Tyr(Bzl)-Gly-Gly-Phe-Met (74937-32-9) → met-enkephalin (58569-55-4)

Conditions	Yield
With methyl-phenyl-thioether In trifluoroacetic acid at 25℃; for 4h; Yield given;

methyl ester of N,O-di-t-butyloxycarbonyl-L-tyrosylglycylglycyl-L-phenylalanyl-L-methionine (81649-52-7) → met-enkephalin (58569-55-4)

Conditions	Yield
With hydrogenchloride; sodium hydroxide 1.) methanol, water, 4 h, 2.) AcOH, 45 min; Yield given. Multistep reaction;

Z-Tyr-Gly-Gly-Phe-Hcy(Bzl)-OBzl (97512-82-8) + methyl iodide (74-88-4) → met-enkephalin (58569-55-4)

Conditions	Yield
With sodium 1.) NH3 liq., -70 deg C, 2.) hexane-NH3, -70 -> -25 deg C, 1 h; Yield given. Multistep reaction;

methionine-enkephalin sulfoxide (60283-51-4) → met-enkephalin (58569-55-4)

Conditions	Yield
With ammonium iodide; dimethylsulfide In trifluoroacetic acid at 0℃;

BocMet-R, Boc-amino acids → met-enkephalin (58569-55-4)

Conditions	Yield
Yield given; Multistep reaction;

phospho-Tyr-Gly-Gly-Phe-Met-OH → met-enkephalin (58569-55-4) + O-phosphono-L-tyrosine (21820-51-9) + L-tyrosine (60-18-4) + [des-tyr1]-methionine enkephalin (61370-88-5)

Conditions	Yield
With aminopeptidase M (EC3.4.11.2); 2-amino-2-hydroxymethyl-1,3-propanediol at 37℃; for 1h; pH=7.02; Kinetics; Hydrolysis;

-enkephalyl-arg6-phe7 → L-arginyl-L-phenylalanine (2047-13-4) + met-enkephalin (58569-55-4)

Conditions	Yield
With angiotensin I converting enzyme In various solvent(s) at 37℃; pH=7.75; Kinetics;

-enkephalyl-arg6-phe7 → YG (673-08-5) + met-enkephalin (58569-55-4) + tyrosylglycylglycine (21778-69-8) + L-tyrosine (60-18-4)

Conditions	Yield
With membrane fraction In various solvents at 37℃; for 1h; pH=7.4; Product distribution; Further Variations:; Reagents;

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + Boc-Pro, Boc-Cys(Bzl), Boc-Asn NPE, Boc-Val → met-enkephalin (58569-55-4)

Conditions

Yield

Multi-step reaction with 8 steps 1: NMM / dimethylformamide / 0.17 h / -15 °C 2: NMM / dimethylformamide / 20 h / -20 °C 3: 90 percent / 1.5 N HCl/AcOH 4: 97 percent / HOBt*H2O, NEt3 / dimethylformamide / 23 h 5: 95 percent / 1.5 N HCl/AcOH / 1 h 6: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 7: 86 percent / 0.5 M NaOH / acetone / 1.5 h 8: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme

Methyl ester of N-t-butyloxycarbonyl-L-phenylalanyl-L-methionine (40290-63-9) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: 90 percent / 1.5 N HCl/AcOH 2: 97 percent / HOBt*H2O, NEt3 / dimethylformamide / 23 h 3: 95 percent / 1.5 N HCl/AcOH / 1 h 4: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 5: 86 percent / 0.5 M NaOH / acetone / 1.5 h 6: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme
Multi-step reaction with 5 steps 1: 98 percent / 4 M HCl / dioxane / 0.75 h 2: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 3: 91 percent / 2 M HCl / acetic acid / 0.75 h 4: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 5: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme
Multi-step reaction with 8 steps 1: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl / 1.) room temp., 5 h, 2.) Et2O 2: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h 2) RT 12h 3: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 4: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h, 2) RT, 12h 5: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 6: 1) 1-β-naphthalenesulphonyloxybenzotriazole, 2) N-methylmorpholine / 1) EtOAc, 1.5h, DMF, RT, 2) RT, 15h 7: 92.23 percent / 2N NaOH / methanol; H2O / 1 h / Ambient temperature 8: 10percentHCl, C6H5OCH3, HS-(CH2)2-SH / dioxane / 1 h / Ambient temperature View Scheme

methyl N-tert-butoxycarbonyl-L-tyrosyldiglycyl-L-phenylalanyl-L-methioninate (60566-44-1) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / 0.5 M NaOH / acetone / 1.5 h 2: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme

N-tert-Butyloxycarbonyl-glycyl-glycyl-L-phenylalanyl-L-methionin-methylester (70035-45-9) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / 1.5 N HCl/AcOH / 1 h 2: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 3: 86 percent / 0.5 M NaOH / acetone / 1.5 h 4: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme
Multi-step reaction with 3 steps 1: 91 percent / 2 M HCl / acetic acid / 0.75 h 2: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 3: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme
Multi-step reaction with 4 steps 1: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 2: 1) 1-β-naphthalenesulphonyloxybenzotriazole, 2) N-methylmorpholine / 1) EtOAc, 1.5h, DMF, RT, 2) RT, 15h 3: 92.23 percent / 2N NaOH / methanol; H2O / 1 h / Ambient temperature 4: 10percentHCl, C6H5OCH3, HS-(CH2)2-SH / dioxane / 1 h / Ambient temperature View Scheme

Boc-Phe-O-COO-isoBu (67729-36-6, 60398-40-5) → met-enkephalin (58569-55-4)

Conditions

Yield

Multi-step reaction with 7 steps 1: NMM / dimethylformamide / 20 h / -20 °C 2: 90 percent / 1.5 N HCl/AcOH 3: 97 percent / HOBt*H2O, NEt3 / dimethylformamide / 23 h 4: 95 percent / 1.5 N HCl/AcOH / 1 h 5: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 6: 86 percent / 0.5 M NaOH / acetone / 1.5 h 7: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme

hydrochloride of methyl ester of glycylglycyl-L-phenylalanyl-L-methionine (70035-46-0) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 2: 86 percent / 0.5 M NaOH / acetone / 1.5 h 3: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme
Multi-step reaction with 2 steps 1: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 2: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme
Multi-step reaction with 3 steps 1: N-methylmorpholine, 2,6-luditine / CH2Cl2; dimethylformamide / 1.) 0 deg C, 1 h, 2.) r. t., 1 h 2: 91 percent / aq. NaOH / dimethylformamide / 6 h 3: 40 percent / aq. HCl / dioxane / 6 h View Scheme
Multi-step reaction with 3 steps 1: 1) 1-β-naphthalenesulphonyloxybenzotriazole, 2) N-methylmorpholine / 1) EtOAc, 1.5h, DMF, RT, 2) RT, 15h 2: 92.23 percent / 2N NaOH / methanol; H2O / 1 h / Ambient temperature 3: 10percentHCl, C6H5OCH3, HS-(CH2)2-SH / dioxane / 1 h / Ambient temperature View Scheme

L-phenylalaninyl-L-methionine methyl ether p-toluenesulfonate → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 97 percent / HOBt*H2O, NEt3 / dimethylformamide / 23 h 2: 95 percent / 1.5 N HCl/AcOH / 1 h 3: 90 percent / HOBt*H2O, NEt3, DCC / dimethylformamide / a) -5 deg C to 0 deg C, 1 h, b) 20 deg C, 24 h 4: 86 percent / 0.5 M NaOH / acetone / 1.5 h 5: 90 percent / 1.3 M HCl/AcOH / 1 h View Scheme

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 7 steps 1: 90 percent / N,N'-dicyclohexylcarbodiimide (DCCI) / tetrahydrofuran / Ambient temperature 2: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 3: 98 percent / 4 M HCl / dioxane / 0.75 h 4: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 5: 91 percent / 2 M HCl / acetic acid / 0.75 h 6: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 7: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme
Multi-step reaction with 4 steps 1: 1.) N-methylmorpholine, isobutyl chloroformate / 1.) THF, -15 deg C, 1 min, 2.) -10 deg C, 30 min; 20 deg C, 2 h 2: 95 percent / 4.1 M HCl / dioxane / 4 h / 20 °C 3: 1.) 4.1 M HCl, isopentyl nitrite, 2.) Et3N / 1.) DMF, -20 deg C, 1 h, 2.) -30 deg C, 1 h; 4 deg C, 21 h 4: 1.) Na / 1.) NH3 liq., -70 deg C, 2.) hexane-NH3, -70 -> -25 deg C, 1 h View Scheme
Multi-step reaction with 9 steps 1: 1)N-methylmorpholine, 1-β-napthalenesulphonyloxybenzotriazole / 1)EtOAc, RT, 1.5h 2) 12h RT 2: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl / 1.) room temp., 5 h, 2.) Et2O 3: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h 2) RT 12h 4: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 5: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h, 2) RT, 12h 6: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 7: 1) 1-β-naphthalenesulphonyloxybenzotriazole, 2) N-methylmorpholine / 1) EtOAc, 1.5h, DMF, RT, 2) RT, 15h 8: 92.23 percent / 2N NaOH / methanol; H2O / 1 h / Ambient temperature 9: 10percentHCl, C6H5OCH3, HS-(CH2)2-SH / dioxane / 1 h / Ambient temperature View Scheme
Multi-step reaction with 8 steps 1.1: N,N-dimethyl-formamide / 20 °C 2.1: 4-methyl-morpholine / N,N-dimethyl-formamide / 0 °C / pH 7 2.2: 4 h / 0 - 20 °C 3.1: hydrogenchloride; methyl-phenyl-thioether; 2-hydroxyethanethiol / 1,4-dioxane / 0.25 h / 20 °C 4.1: 4-methyl-morpholine / N,N-dimethyl-formamide / 0 °C / pH 7 4.2: 0 °C 4.3: 4 h / 0 - 20 °C 5.1: hydrogenchloride; methyl-phenyl-thioether; 2-hydroxyethanethiol / 1,4-dioxane / 1 h / 20 °C 6.1: 4-methyl-morpholine / N,N-dimethyl-formamide / 0 °C 6.3: 4 h / 0 - 20 °C 7.1: palladium 10% on activated carbon / methanol / 0.33 h / 20 °C 8.1: hydrogenchloride; methyl-phenyl-thioether; 2-hydroxyethanethiol / 1,4-dioxane / 0.5 h / 0 °C View Scheme

hydrochloride of methyl ester of L-phenylalanyl-L-methionine (40290-65-1) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 2: 91 percent / 2 M HCl / acetic acid / 0.75 h 3: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 4: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme
Multi-step reaction with 7 steps 1: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h 2) RT 12h 2: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 3: 1) N-methylmorpholine, 1-β-naphthalenesulphonyloxybenzotriazole / 1) EtOAc, DMF, 1.5h, 2) RT, 12h 4: 1.) HCO2H, PhOMe, HS-(CH2)2-SH, 2.) HCl 5: 1) 1-β-naphthalenesulphonyloxybenzotriazole, 2) N-methylmorpholine / 1) EtOAc, 1.5h, DMF, RT, 2) RT, 15h 6: 92.23 percent / 2N NaOH / methanol; H2O / 1 h / Ambient temperature 7: 10percentHCl, C6H5OCH3, HS-(CH2)2-SH / dioxane / 1 h / Ambient temperature View Scheme

O-(t-butyloxycarbonyl-L-phenylalanyl)-2-pyridylmethylketoxime (81638-94-0) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 2: 98 percent / 4 M HCl / dioxane / 0.75 h 3: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) THF, 24 h 4: 91 percent / 2 M HCl / acetic acid / 0.75 h 5: 1.) NH3, 2.) AcOH / 1.) CHCl3, 5 min, 2.) DMF, THF, 24 h 6: 1.) 2 M NaOH, 2.) 2M HCl / 1.) methanol, water, 4 h, 2.) AcOH, 45 min View Scheme

N-benzyloxycarbonyl-O-benzyl-L-tyrosine (86827-18-1, 92455-53-3, 16677-29-5) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: dicyclohexylcarbodi-imide 4: thioanisole / trifluoroacetic acid / 4 h / 25 °C View Scheme

N-(O-benzyl-N-benzyloxycarbonyl-L-tyrosyl)-glycine ethyl ester (21869-36-3) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 3 steps 3: thioanisole / trifluoroacetic acid / 4 h / 25 °C View Scheme

Z-Tyr(Bzl)-Gly-N2H3 (74916-75-9) → met-enkephalin (58569-55-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: thioanisole / trifluoroacetic acid / 4 h / 25 °C View Scheme

fluorescein isothiocyanate (3326-32-7, 27072-45-3) + met-enkephalin (58569-55-4) → C48H46N6O12S2

Conditions	Yield
With N-ethylmorpholine; In N,N-dimethyl-formamide at 20℃; for 24h;

Upstream product

• 60283-51-4 methionine-enkephalin sulfoxide 
• 74937-32-9 Z-Tyr(Bzl)-Gly-Gly-Phe-Met 
• 4976-72-1 tert-butyl (2S)-2-amino-4-methylsulfanylbutanoate 
• 1188307-69-8 C₄₁H₅₀N₆O₁₇S 
• 97512-82-8 Z-Tyr-Gly-Gly-Phe-Hcy(Bzl)-OBzl 
• 74-88-4 methyl iodide 
• 81649-52-7 methyl ester of N,O-di-t-butyloxycarbonyl-L-tyrosylglycylglycyl-L-phenylalanyl-L-methionine 
• 148715-90-6 N-(diphenylphosphinoyl)tyrosylglycylglycylphenylalanylmethionine 
• 82362-16-1 Boc-Tyr-Gly-Gly-Phe-Met-OBu^t 
• 129398-74-9 Boc-Tyr(Mtb)-Gly-Gly-Phe-Met-OMtb 
• 129398-68-1 Boc-Tyr(Cl₂Bzl)-Gly-Gly-Phe-Met-OBzl 
• 62530-43-2 Boc-Tyr(tert.-Bu)-Gly-Gly-Phe-Met 
• 59481-77-5 boc-Tyr-Gly-Gly-Phe-Met-OH 

Downstream Products

• 59481-77-5 boc-Tyr-Gly-Gly-Phe-Met-OH 
• 60283-51-4 methionine-enkephalin sulfoxide 
• 60117-26-2 C₂₇H₃₅N₅O₈S 
• 75525-04-1 YGGFMYGGFM 
• 1334396-63-2 Ac-AAAYGGFM 

Relevant articles and documents

Neutrophil-mediated oxidation of enkephalins via myeloperoxidase-dependent addition of superoxide

Neutrophils play a major role in acute inflammation in part by generating superoxide and an array of other reactive species. These white blood cells also contribute to protection against inflammatory pain by releasing opioid peptides. The biochemical interactions of enkephalins with neutrophil-derived oxidants are not well understood. In this investigation we reveal that neutrophils use myeloperoxidase to oxidize enkephalins to their corresponding tyrosyl free radicals, which react preferentially with the superoxide to form a hydroperoxide. In methionine enkephalin, rapid intramolecular oxygen transfer from the hydroperoxide to the Met sulfur results in the formation of a sulfoxide derivative. This reaction may occur at sites of inflammation where enkephalins are released and neutrophils generate large amounts of superoxide. Hydroperoxide formation destroys the aromatic character of the Tyr residue by forming a bicyclic structure via conjugate addition of the terminal amine to the phenol ring. As the N-terminal Tyr and its amino group are essential for their opiate activity, we hypothesize that oxidative modification of this residue should affect the analgesic activity of enkephalins.

IMPROVED DEPROTECTION IN SOLID PHASE PEPTIDE SYNTHEIS: QUANTITATIVE REDUCTION OF METHIONINE SULFOXIDE TO METHIONINE DURING HF CLEAVAGE

The reduction of methionine sulfoxide residues in peptides was found to be quantitative by treatment with a low concentration of HF in dimethyl-sulfide (HF:dimethylsulfide, 1:3, v/v).The reduction was dependent on the acidity function of HF and was optimal with an HF concentration between 25percent and 40percent.The low HF concentration cleavage reagent also deprotected most of the benzyl alcohol-derived protecting groups.

Sustainable Peptide Synthesis Enabled by a Transient Protecting Group

The growing interest in synthetic peptides has prompted the development of viable methods for their sustainable production. Currently, large amounts of toxic solvents are required for peptide assembly from protected building blocks, and switching to water as a reaction medium remains a major hurdle in peptide chemistry. We report an aqueous solid-phase peptide synthesis strategy that is based on a water-compatible 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) protecting group. This approach enables peptide assembly under aqueous conditions, real-time monitoring of building block coupling, and efficient postsynthetic purification. The procedure for the synthesis of all natural and several non-natural Smoc-protected amino acids is described, as well as the assembly of 22 peptide sequences and the fundamental issues of SPPS, including the protecting group strategy, coupling and cleavage efficiency, stability under aqueous conditions, and crucial side reactions.

Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid

The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2?+?2?+?1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.

Nicotinoyl peptide derivatives and cosmetic composition comprising the same

The present invention relates to nicotinoyl peptide derivatives, wherein neuropeptides are connected to nicotinic acid, and a cosmetic composition comprising the same. The peptide derivatives according to the present invention have good collagen generation and anti-inflammatory activities to show an excellent anti-wrinkle effect, little cytotoxicity, water-solubility, and good stability during long-term storage. Therefore, they can be effectively used for preparing an anti-aging cosmetic composition.

Simple, economical and flexible apparatus for solid phase peptide synthesis

Solid phase peptide synthesis basically involves repetitive deblocking and coupling reactions. In order to make these repetitive operations fast and convenient, the deblocking and coupling reactions are carried out in specially designed apparatus, which are called solid phase peptide synthesis apparatus. These apparatus are expensive, hence unaffordable for many laboratories. In addition, these apparatus lack the operational flexibility for varying reaction parameters such as reaction time, temperature, pressure, sonication, microwave irradiation, etc. In order to make peptide synthesis convenient and flexible with respect to reaction conditions and affordable for many laboratories, a two-vessel approach has been proposed. In this approach, coupling reaction is carried out in a round bottom flask with overhead stirrer, and the filtration (work-up) is carried out in a specially designed filtration-vessel. Using the two-vessel approach, D-Met-enkephalins (pentapeptides, Tyr-Gly-Gly-Phe-D-Met) and some of its derivatives involving lengthy reactions have been synthesized on Merrifield resin. This approach is very convenient for studying variations in reaction conditions and is good for synthesizing short peptides (10 amino acids). By this approach 1-100 g resin can be handled in a laboratory without any additional cost. This approach can be extrapolated to solid phase syntheses as well.

Reduction of methionine sulfoxide with NH4I/TFA: Compatibility with peptides containing cysteine and aromatic amino acids

The reduction of methionine sulfoxide with ammonium iodide in trifluoroacetic acid has been studied in peptides containing cysteine, histidine, tyrosine or tryptophan residues. While histidine and tyrosine have proved to be stable under the experimental conditions, cysteine is oxidized to cystine and tryptophan dimerizes to form 2-indolylindolenine derivatives. The use of methyl sulfide to increase the reduction rate minimizes the problem and protection of indole ring with the formyl group avoids the side reaction for this amino acid.

Convenient high yielding gram scale solution synthesis of methionine-enkephalin

A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Gly-Gly-Phe-Met, has been elaborated. Classical solution peptide chemistry methods without protection of amino acid side-chain functions and l+(2+2) segment condensation were used. A nine-step synthesis from commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was found to be 99.0-100% by HPLC. The process has been used to prepare greater than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation was observed during saponification of Boc-TyrGly-Gly-Phe-Met-OMe and minimised.

Effects of three peptidase inhibitors, amastatin, captopril and phosphoramidon, on the hydrolysis of [Met5]-enkephalin-Arg6-Phe7 and other opioid peptides

The contents of [Met5]-enkephalin-Arg6-Phe7 (met-enk-RF) and its six hydrolysis products: Y, YG, YGG, YGGF, YGGFM, and YGGFMR were estimated after incubating met-enk-RF with either a guinea-pig ileal or striatal membrane fraction for various times at 37°C. After 45 min incubation with either ileal or striatal membranes, met-enk-RF was completely hydrolyzed, yielding Y as the major product. Incubation with either membrane preparation for 60 min in the presence of the aminopeptidase inhibitor amastatin hydrolyzed 90 or 92% of met-enk-RF, respectively, with YGG being the major product. If the dipeptidyl carboxypeptidase I inhibitor captopril is also included in the incubation, met-enk-RF hydrolysis decreases by about half for both membranes, with YGG remaining the major product. Inclusion of three peptidase inhibitors, amastatin, captopril, and phosphoramidon (inhibition of endopeptidase-24.11) further reduced met-enkhydrolysis, with 87% or more remaining intact. This shows that met-enk-RF was mainly hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal membranes. Additionally, estimations of [Leu5]-enkephalin (leu-enk), α- and β-neoendorphins (α- and β-neoends), and dynorphin B (dyn B) contents after incubating the individual peptides with striatal membrane for 60 min in the presence of the three peptidase inhibitors showed that 98, 32, 5, and 23%, respectively, remained intact. Our previous studies together with the data obtained here show that one group of endogenous opioid peptides: met-enk, leu-enk, met-enk-RF, met-enk-RGL, and dyn A-(1-8) are largely or almost exclusively hydrolyzed by the three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I, and phosphoramidon-sensitive endopeptidase-24.11, and indicate that an unidentified fourth enzyme(s) is involved in the hydrolysis of another group of peptides: α-neoend, β-neoend, and dyn B.

Differences in the hydrolysis of enkephalin congeners by the two domains of angiotensin converting enzyme

The hydrolysis of enkephalin (Enk) congeners by the isolated N- (N-ACE) and C-domain of angiotensin I converting enzyme (ACE) and by the two-domain somatic ACE was investigated. Both Leu5- and Met5-Enk were cleaved faster by the C-domain than by N-ACE; rates with somatic ACE were 1600 and 2500 nmol/min/nmol enzyme with both active sites being involved. Substitution of Gly2 by D-Ala2 reduced the rate to 1/3rd to 1/7th of that of the Enks. N- ACE cleaved Met5-Enk-Arg6-Phe7 faster than the C-domain, probably with the highest turnover number of any naturally occurring ACE substrate (7600 min- 1). This heptapeptide is also hydrolyzed in the absence of Cl-, but the activation by Cl- is unique; Cl- enhances the hydrolysis of the heptapeptide by N-ACE but inhibits it by the C-domain, yielding about a 5- fold difference in the turnover number at physiological pH. This difference may result in the predominant role of the N-domain in converting Met5-Enk- Arg6-Phe7 to Enk in vivo.