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 - DFBPANTH0001(Antithrombotic peptide)

DFBP ID	DFBPANTH0001
Peptide sequence	MAIPPKKNQDK
Type	Native peptide
Peptide/Function name	Antithrombotic peptide, Casoplatelin

Function-activity relationship

Main bioactivity	Antithrombotic activity
Otheir bioactivity	N.D

Calculated physicochemical properties

Three-letter amino acid

Met-Ala-Ile-Pro-Pro-Lys-Lys-Asn-Gln-Asp-Lys

Single-letter amino acid

MAIPPKKNQDK

Peptide length

Peptide mass

Experimental mass	Theoretical mass
N.D	1269.52 Da ^c

Net charge

0.00 ^c

Isoelectric point (pI)

10.32 ^c

IC₅₀

N.D

pIC₅₀

N.D

GRAVY

-1.5636^c

Hydrophilic residue ratio

45.45%^c

Peptide calculator

Peptide source & Food-borne protein(s) search

Classification	Animal
Organism/Source	Cow milk protein
Precursor protein	κ-Casein
Residue position	f(106-116)
Precursor protein(s) search	Source.1: DFBPPR7715 ---- Milk proteins ---- Kappa-casein Source.2: DFBPPR8492 ---- Milk proteins ---- Kappa-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

Antithrombotic activity

The natural undecapeptide MAIPPKKNQDK inhibited the binding of ¹²⁵I-fibrinogen to ADP-treated platelets in a concentration-dependent manner. The concentration of the peptide required for 40% and 75% inhibition of fibrinogen binding was 120 μM and 240 μM, respectively. In parallel, the peptide inhibited the ADP-induced platelet aggregations: its behaviour was similar to that of the structurally related C-terminal dodecapeptide of human fibrinogen γ-chain (400-411). Similar results were obtained with the synthetic peptide.
The peptide is inhibitors of both, the aggregation of ADP-activated platelets and binding of human fibrinogen γ-chain to a specific receptor region on the platelet sufrace. The peptide has no inhibition on chymosin for casein^[4].
The interacting region of the fibrinogen γ-chain in platelet aggregation is the C-terminal dodecapeptide sequence that itself possesses similar inhibiting effects ^[5].
Molecular docking of peptide and thrombin (PDB: 2BVR): Affinity was observed for MAIPPKKNQDK with ‘‘-CDOCKER Energy” values of 131.931 kcal/mol, the peptide was a potential antithrombotic peptide (Antithrombotic activity of synthetic peptides was not determined) ^[7].

Table 1. Milk anti-aggregating peptides. Comparison with fibrinogen peptides ^[6].
Peptides	Inhibition (IC₅₀, μM)
Peptides	ADP-Induced human platelet aggregation	ADP-Induced [¹²⁵I]fibrinogen binding to human platelets
MAIPPKKNQDK	60	120
NQDK	400	﹣
MAIPPKK	> 1600	﹣

Specific target protein(s)

Specific Target Protein(s):
Fibrinogen gamma chain
Potential Target Protein(s):
Integrin beta-3
Integrin alpha-IIb
Integrin alpha-2
Platelet glycoprotein IX
Platelet glycoprotein Ib alpha chain
Platelet glycoprotein Ib beta chain
Platelet glycoprotein 4

Taste properties & Structure

Bitterness

Literature report	N.D
Bitter prediction tools	No prediction can be made about the peptide bitterness. ^prediction

SMILES

N[C@@]([H])(CCSC)C(=O)N[C@@]([H])(C)C(=O)N[C@@]([H])([C@]([H])(CC)C)C(=O)N1[C@@]([H])(CCC1)C(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])(CCCCN)C(=O)N[C@@]([H])(CCCCN)C(=O)N[C@@]([H])(CC(=O)N)C(=O)N[C@@]([H])(CCC(=O)N)C(=O)N[C@@]([H])(CC(=O)O)C(=O)N[C@@]([H])(CCCCN)C(=O)O

Preparation method

Mode of preparation	Enzymatic hydrolysis
Enzyme(s)/starter culture	Chymosin digestion of cow κ-caein releases the κ-caseinoglycopeptide, the C-terminal part of κ-casein (residues 106-169). And then the κ-caseinoglycopeptide was digested with trypsin.

Stability & Cytotoxicity

Peptide stability

Literature report:	N.D
EHP-Tool:	Enzymatic Hydrolysis Prediction Tool (EHP-Tool)

Peptide cytotoxicity

Literature report:	N.D
Prediction:	ToxinPred

Additional information

Sixty percent of the peptides identified in the casein hydrolysate showed good thrombin inhibitory activity. This method can be further developed to facilitate the rational production of bioactive peptides for their utilization in various functional food applications ^[7].

Database cross-references

[D1]

[D2]

[D3]

[D4]

Reference(s)

Primary literature	Jollès P, Lévy-Toledano S, Fiat AM, Soria C, Gillessen D, Thomaidis A, Dunn FW, Caen JP. Analogy between fibrinogen and casein. Effect of an undecapeptide isolated from kappa-casein on platelet function. Eur J Biochem. 1986 Jul 15;158(2):379-82. PMID: 3732274 DOI: 10.1111/j.1432-1033.1986.tb09764.x
Other literature(s)	[1] Park Y W. Bioactive Components in Milk and Dairy Products[M]. 2009. [2] Schlimme E, Meisel H. Bioactive peptides derived from milk proteins. Structural, physiological and analytical aspects.[J]. Nahrung, 2010, 39(1):1-20. [3] Xu, Ruo‐Jun. Bioactive Peptides in Milk and their Biological and Health Implications[J]. Food Reviews International, 1998, 14(1):1-16. [4] Fiat A M, Levytoledano S, Caen J P, et al. Biologically active peptides of casein and lactotransferrin implicated in platelet function.[J]. Journal of Dairy Research, 1989, 56(3):351-355. [5] Kloczewiak M, Timmons S, Lukas T J, et al. Platelet receptor recognition site on human fibrinogen. Synthesis and structure-function relationship of peptides corresponding to the carboxy-terminal segment of the gamma chain[J]. Biochemistry, 1984, 23(8):1767-74. [6] Fiat A M, Migliore-Samour D, Jollã¨S P, et al. Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities[J]. Journal of Dairy Science, 1993, 76(1):301-310. [7] Tu M, Feng L, Wang Z, et al. Sequence analysis and molecular docking of antithrombotic peptides from casein hydrolysate by trypsin digestion[J]. Journal of Functional Foods, 2017, 32:313-323.
PubDate	1986