Opioid peptides

Most opioid peptides begin with Tyr-Gly-Gly-Phe followed by methionine or leucine, the enkephalin sequence, which recurs at the N-terminus of longer members such as β-endorphin and dynorphin A. The endomorphins are tetrapeptide amides without that motif, and nociceptin begins with phenylalanine instead of tyrosine. Leu-enkephalin is the reference sequence here.

Members compared

Calculated from each structure

Peptide	Residues	Formula	Monoisotopic mass (Da)	Charge, pH 7	pI	Termini
Endomorphin-1	4	C34H38N6O5	610.2904	1.0	9.35	free amine; amide
Endomorphin-2	4	C32H37N5O5	571.2795	1.0	9.35	free amine; amide
Leu-enkephalin	5	C28H37N5O7	555.2693	0.0	6.09	free amine; free acid
Met-enkephalin	5	C27H35N5O7S	573.2257	0.0	6.09	free amine; free acid
Dynorphin A (1–13)	13	C75H126N24O15	1,602.9834	5.0	12.25	free amine; free acid
Nociceptin	17	C79H129N27O22	1,807.9805	4.0	12.53	free amine; free acid
β-Endorphin	31	C158H251N39O46S	3,462.8221	3.0	10.17	free amine; free acid

Sequences and relationships

Each member's sequence in three-letter code, and how it relates to Leu-enkephalin, worked out position by position from the structures. Members with no entry in the last column are not direct sequence relatives of Leu-enkephalin.

Relationship to Leu-enkephalin

Peptide	Sequence	Relationship
Endomorphin-1	H-Tyr-Pro-Trp-Phe-NH2	Residues 1–4 of Leu-enkephalin, with 2 substitutions: Gly2→Pro, Gly3→Trp; C-terminus amide (reference: free acid)
Endomorphin-2	H-Tyr-Pro-Phe-Phe-NH2	Residues 1–4 of Leu-enkephalin, with 2 substitutions: Gly2→Pro, Gly3→Phe; C-terminus amide (reference: free acid)
Leu-enkephalin	H-Tyr-Gly-Gly-Phe-Leu-OH	Reference sequence
Met-enkephalin	H-Tyr-Gly-Gly-Phe-Met-OH	Same length as Leu-enkephalin, with 1 substitution: Leu5→Met
Dynorphin A (1–13)	H-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH	—
Nociceptin	H-Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln-OH	—
β-Endorphin	H-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu-OH	—

Shared analytical features

The sequence-specific variants from each member's entry, counted across the family: what an HPLC or mass spectrometry result for these peptides is most often read against.

Variants by number of members

Variant	Members
Asparagine deamidation	2 of 7: Nociceptin, β-Endorphin
C-terminal amide	2 of 7: Endomorphin-1, Endomorphin-2
Glutamine deamidation	2 of 7: Nociceptin, β-Endorphin
Methionine oxidation	2 of 7: Met-enkephalin, β-Endorphin
Tryptophan oxidation	1 of 7: Endomorphin-1

Every member can also carry the synthesis-related variants common to all synthetic peptides, described in How synthetic peptides are made.

Pairs compared in detail

• Leu-enkephalin and Met-enkephalin compared
• Endomorphin-1 and Endomorphin-2 compared

Sources & Further Reading

1. Prohaska T, Irrgeher J, Benefield J, Böhlke JK, Chesson LA, Coplen TB, et al. Standard atomic weights of the elements 2021 (IUPAC Technical Report). Pure and Applied Chemistry 2022;94(5):573–600. doi:10.1515/pac-2019-0603
2. Wang M, Huang WJ, Kondev FG, Audi G, Naimi S. The AME 2020 atomic mass evaluation (II). Tables, graphs and references. Chinese Physics C 2021;45(3):030003. doi:10.1088/1674-1137/abddaf
3. Rice P, Longden I, Bleasby A. EMBOSS: the European Molecular Biology Open Software Suite. Trends in Genetics 2000;16(6):276–277. doi:10.1016/S0168-9525(00)02024-2
4. Pace CN, Vajdos F, Fee L, Grimsley G, Gray T. How to measure and predict the molar absorption coefficient of a protein. Protein Science 1995;4(11):2411–2423. doi:10.1002/pro.5560041120
5. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology 1982;157(1):105–132. doi:10.1016/0022-2836(82)90515-0
6. Meija J, Coplen TB, Berglund M, Brand WA, De Bièvre P, Gröning M, et al. Isotopic compositions of the elements 2013 (IUPAC Technical Report). Pure and Applied Chemistry 2016;88(3):293–306. doi:10.1515/pac-2015-0503
7. Roepstorff P, Fohlman J. Letter to the editors: proposal for a common nomenclature for sequence ions in mass spectra of peptides. Biomedical Mass Spectrometry 1984;11(11):601. doi:10.1002/bms.1200111109
8. Biemann K. Contributions of mass spectrometry to peptide and protein structure. Biomedical and Environmental Mass Spectrometry 1988;16(1–12):99–111. doi:10.1002/bms.1200160119
9. Geiger T, Clarke S. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. Journal of Biological Chemistry 1987;262(2):785–794. doi:10.1016/S0021-9258(19)75855-4
10. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6
11. D'Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, et al. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012

Cosmic Peptides. (2026, October 25). Opioid peptides. Cosmic Peptides Research Library. Retrieved October 26, 2026, from https://cosmicpeptides.com/research/peptides/families/opioid

@misc{cosmicpeptides_research_peptides_families_opioid,
  author       = {{Cosmic Peptides}},
  title        = {Opioid peptides},
  howpublished = {Cosmic Peptides Research Library},
  year         = {2026},
  month        = oct,
  url          = {https://cosmicpeptides.com/research/peptides/families/opioid},
  urldate      = {2026-10-26},
  note         = {Last reviewed 2026-10-25}
}

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