Endomorphin-1 and Endomorphin-2 compared

The two endomorphins are tetrapeptide amides that differ only at position 3: tryptophan in endomorphin-1, phenylalanine in endomorphin-2.

Sequences side by side

Aligned from residue 1: 3 positions identical, 1 substituted. In each column the upper residue is Endomorphin-1's and the lower is Endomorphin-2's. Substituted positions are highlighted.

Both have the same termini: free amine and amide.

Calculated properties

Calculated from each structure

Property	Endomorphin-1	Endomorphin-2	Difference (Endomorphin-2 − Endomorphin-1)
Residues	4	4	0
Molecular formula	C34H38N6O5	C32H37N5O5
Monoisotopic mass (Da)	610.2904	571.2795	−39.0109
Average mass (g/mol)	610.72	571.68	−39.04
Net charge at pH 7	1.0	1.0	0.0
Isoelectric point	9.35	9.35	0.00
Hydropathy (GRAVY)	-0.25	0.67	+0.92
ε280 (M−1 cm−1)	6,990	1,490

Telling them apart by mass spectrometry

The monoisotopic masses differ by 39.0109 Da, which any routine mass spectrometer resolves.

Expected protonated ions (monoisotopic m/z)

Ion	Endomorphin-1	Endomorphin-2
[M+H]+	611.2976	572.2867
[M+2H]2+	306.1525	286.6470

Telling them apart by HPLC

Endomorphin-2 is the more hydrophobic by the Kyte–Doolittle average (a difference of 0.92), so in reversed-phase HPLC it would usually be expected to elute later. Retention depends on the whole molecule and on the method, so the order is confirmed by running both, or by mass spectrometry of each peak.

Analytical variants each can form

The sequence-specific variants from each entry. A variant only one of them can form is a quick way to tell which is which, and a reminder of what to look for in each.

Sequence-specific variants

Variant	Mass change	Endomorphin-1	Endomorphin-2
Tryptophan oxidation	+15.995 or +31.990 Da	Yes	No
C-terminal amide	free-acid variant +0.984 Da	Yes	Yes

Full details, with isotope patterns and fragment ions, are on each entry: Endomorphin-1 and Endomorphin-2. Both are compared with the rest of their family on the family page.

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). Endomorphin-1 and Endomorphin-2 compared. Cosmic Peptides Research Library. Retrieved October 26, 2026, from https://cosmicpeptides.com/research/peptides/compare/endomorphin-1-vs-endomorphin-2

@misc{cosmicpeptides_research_peptides_compare_endomorphin_1_vs_endomorphin_2,
  author       = {{Cosmic Peptides}},
  title        = {Endomorphin-1 and Endomorphin-2 compared},
  howpublished = {Cosmic Peptides Research Library},
  year         = {2026},
  month        = oct,
  url          = {https://cosmicpeptides.com/research/peptides/compare/endomorphin-1-vs-endomorphin-2},
  urldate      = {2026-10-26},
  note         = {Last reviewed 2026-10-25}
}

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