Peptide properties

1Top 2Function-activity relationship 3Calculated physicochemical properties 4Peptide source & Food-borne protein(s) search 5Biological/Functional activity & target protein 6Taste properties & Structure 7Preparation method 8Stability & Cytotoxicity 9Additional information 10Database cross-references 11Reference(s)

List of peptide properties

DFBP ID - DFBPOPIO0011(Opioid peptide)

DFBP ID	DFBPOPIO0011
Peptide sequence	YPFPGPI
Type	Native peptide
Peptide/Function name	Opioid peptide, β-Casomorphin-7

Function-activity relationship

Main bioactivity	Opioid activity
Otheir bioactivity	ACE-inhibitory activity ^[D1], Antithrombotic activity ^[D2], Multifunctional activity ^[D3]

Calculated physicochemical properties

Three-letter amino acid

Tyr-Pro-Phe-Pro-Gly-Pro-Ile

Single-letter amino acid

YPFPGPI

Peptide length

Peptide mass

Experimental mass	Theoretical mass
N.D	789.92 Da ^c

Net charge

0.00 ^c

Isoelectric point (pI)

5.92 ^c

IC₅₀

N.D

pIC₅₀

N.D

GRAVY

0.1143^c

Hydrophilic residue ratio

85.71%^c

Peptide calculator

Peptide source & Food-borne protein(s) search

Classification	Animal
Organism/Source	Cheese (Cheddar, Swiss, Brie, Limburger, Blue), Bovine milk protein^[2,3]
Precursor protein	β-Casein
Residue position	f(60-66)
Precursor protein(s) search	Source.1: DFBPPR7718 ---- Milk proteins ---- Beta-casein Source.2: DFBPPR8489 ---- Milk proteins ---- Beta-casein
Link-research Inductive analysis	There are no literature reports on the discovery of this sequence in other food-source proteins.

Biological/Functional activity & target protein

Opioid activity

The heptapeptide YPFPGPI showed potently opioid activity for μ-opiate receptor. After carboxypeptidase digestion a pentapeptide, YPFPG, could be isolated; this peptide showed a higher opioid activity than the heptapeptide. As shown in table 1.

Table 1 Opioid activity of peptides
Peptide	IC₅₀ (uM)			IC₅₀ MVD	Activity	References
	RA^a	GPI^b	MVD^c	IC₅₀ GPI
YPFPGPI	－	55	> 500	－	Opioid agonist	－
	This peptide showed potently active as opioid agonist (IC₅₀ = 14.0 umol/l) and has been characterized as μ-type ligands					[2]
	30	6.9	nd	－		[3]
	Opioid peptides are opioid μ-receptor ligands (Receptor affinity IC₅₀ = 3.6 μM) with agonistic activities (Opioid activity in GPI assay IC₅₀ = 3.2 μM).					[14]

^a Radioreceptor assay in the presence of 1 nM [³H]naloxone.
^b Guinea pig ileum assay.
^c Mouse vas deferens assay. nd, not determined.

Specific target protein(s)

Specific Target Protein(s):
Mu-type opioid receptor

Taste properties & Structure

Bitterness

Literature report	Bitter peptide according to BIOPEP database of sensory peptides and amino acids^[D4].
Bitter prediction tools	Bitter taste ^prediction

SMILES

N[C@@]([H])(Cc1ccc(O)cc1)C(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])(Cc1ccccc1)C(=O)N1[C@@]([H])(CCC1)C(=O)NCC(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])([C@]([H])(CC)C)C(=O)O

Preparation method

Mode of preparation	Enzymatic hydrolysis
Enzyme(s)/starter culture	(1) Hydrolysis with Pepsin. (2) To simulate in vivo digestion, bovine β-casein was digested by pepsin, pancreatin and then by leucine aminopeptidase (LAP) ^[14].

Stability & Cytotoxicity

Peptide stability

Literature report:	The opioid peptide was highly resistant towards proteolysis, even by pronase.
EHP-Tool:	Enzymatic Hydrolysis Prediction Tool (EHP-Tool)

Peptide cytotoxicity

Literature report:	N.D
Prediction:	ToxinPred

Additional information

The sequence of bovine β-casein (59-81) is -LVYPFPGPI-Pro⁶⁷/His⁶⁷-NSLPQNIPPLTQTP- ^[14].

Database cross-references

DFBP

[D1]	DFBPACEI0345
[D2]	DFBPANTH0169
[D3]	DFBPMUFU0103

[D4]

[D5]

[D6]

[D7]

Reference(s)

Primary literature	Henschen A, Lottspeich F, Brantl V, Teschemacher H. Novel opioid peptides derived from casein (beta-casomorphins). II. Structure of active components from bovine casein peptone. Hoppe Seylers Z Physiol Chem. 1979 Sep;360(9):1217-24. PMID: 511111
Other literature(s)	[1] Park Y W. Bioactive Components in Milk and Dairy Products[M]. 2009. [2] Meisel H, Fitzgerald R J. Opioid peptides encrypted in intact milk protein sequences.[J]. British Journal of Nutrition, 2000, 84(S1):27-31. [3] Yoshikawa M, Tani F, Yoshimura T, et al. Opioid Peptides from Milk Proteins[J]. Journal of the Agricultural Chemical Society of Japan, 1986, 50(9):2419-2421. [4] Jarmołowska B, Kostyra E, Krawczuk S, et al. β‐Casomorphin‐7 isolated from Brie cheese[J]. Journal of the Science of Food & Agriculture, 1999, 79(13):1788–1792. [5] Muehlenkamp M R, Warthesen J J. Beta-casomorphins: analysis in cheese and susceptibility to proteolytic enzymes from Lactococcus lactis ssp. cremoris.[J]. Journal of Dairy Science, 1996, 79(1):20. [6] Saito T, Nakamura T, Kitazawa H, et al. Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese[J]. Journal of Dairy Science, 2000, 83(7):1434-40. [7] Brantl V,Teschemacher H,Henschen A et al. Novel opioid peptides derived from casein (beta-casomorphins). I. Isolation from bovine casein peptone.[J] .Hoppe-Seyler's Z. Physiol. Chem., 1979, 360(9): 1211-6. [8] Lottspeich F, Henschen A, Brantl V, et al. Novel opioid peptides derived from casein (beta-casomorphins). III. Synthetic peptides corresponding to components from bovine casein peptone[J]. Hoppe-Seyler´s Zeitschrift für physiologische Chemie, 1980, 361(2):1835-1840. [9] Koch G, Wiedemann K, Teschemacher H. Opioid activities of human beta-casomorphins[J]. Naunyn Schmiedebergs Arch Pharmacol, 1985, 331(4):351-354. [10] Brantl V, Teschemacher H, Blã¤Sig J, et al. Opioid activities of beta-casomorphins[J]. Life Sciences, 1981, 28(17):1903-1909. [11] Kostyra E, Sienkiewiczszłapka E, Jarmołowska B, et al. Opioid peptides derived from milk proteins.[J]. Polish Journal of Food & Nutrition Sciences, 2004. [12] Teschemacher H., Schweigerer I., Opioid peptides: do have immunological significance? Trends Pharmacol. Sci., 1985, 6, 368–370. [13] Nyberg F, Sanderson K, Glämsta E L. The hemorphins: a new class of opioid peptides derived from the blood protein hemoglobin.[J]. Peptide Science, 1997, 43(2):147-156. [14] Jinsmaa Y, Yoshikawa M. Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein.[J]. Peptides, 1999, 20(8):957.
PubDate	1979