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 - DFBPANTH0006(Antithrombotic peptide)

DFBP ID	DFBPANTH0006
Peptide sequence	MAIPPKK
Type	Native peptide
Peptide/Function name	Antithrombotic peptide, Casoplatelin

Function-activity relationship

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

Calculated physicochemical properties

Three-letter amino acid

Met-Ala-Ile-Pro-Pro-Lys-Lys

Single-letter amino acid

MAIPPKK

Peptide length

Peptide mass

Experimental mass	Theoretical mass
N.D	784.02 Da ^c

Net charge

0.00 ^c

Isoelectric point (pI)

10.59 ^c

IC₅₀

N.D

pIC₅₀

N.D

GRAVY

-0.4000^c

Hydrophilic residue ratio

71.43%^c

Peptide calculator

Peptide source & Food-borne protein(s) search

Classification	Animal
Organism/Source	Bovine milk protein
Precursor protein	κ-Casein
Residue position	f(106-112)
Precursor protein(s) search	Source.1: DFBPPR7686 ---- Milk proteins ---- Kappa-casein Source.2: DFBPPR7695 ---- Milk proteins ---- Kappa-casein Source.3: DFBPPR7715 ---- Milk proteins ---- Kappa-casein Source.4: DFBPPR8492 ---- Milk proteins ---- Kappa-casein
Link-research Inductive analysis	Link 1: DFBPANTH0053----Sheep milk protein----κ-Casein Link 2: DFBPANTH0162----Bovine milk (Bos taurus)----κ-Casein

Biological/Functional activity & target protein

Antithrombotic activity

(1) The synthetic peptide MAIPPKK inhibited the platelet aggregation but its effect was much lower than that induced by the undecapeptide (MAIPPKKNQDK). For the MAIPPKK very high concentrations (800-1600 μM) were required in order to inhibit only 35% of the platelet aggregation which was an unspecific effect. At these concentrations the MAIPPKK had no influence on fibrinogen binding. The effect of the natural peptide was similar (data not shown). So the MAIPPKK can be considered as non-inhibitory on platelet aggregation taking into account the high unspecific concentrations (800-1600 μM).
(2) 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^[4].
(3) The interacting region of the fibrinogen γ-chain in platelet aggregation is the C-terminal dodecapeptide sequence that itself possesses similar inhibiting effects ^[5].
(4) The two smaller tryptic peptide MAIPPKK and NQDK contained in the undecapeptide (MAIPPKKNQDK) have a much lower effect on platelet aggregation and do not inhibit fibrinogen binding, as shown in Table 1 ^[6].

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

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	Bitter taste ^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)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

The peptide was also found in sheep milk proteins^{[D2, 3]}.

Database cross-references

DFBP

[D1]	DFBPACEI0291
[D2]	DFBPANHY0543
[D3]	DFBPMUFU0393

[D4]

[D5]

[D6]

[D7]

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] Qian Z Y, Jollès P, Miglioresamour D, et al. Sheep kappa-casein peptides inhibit platelet aggregation.[J]. Biochimica Et Biophysica Acta, 1995, 1244(2–3):411-417. [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.
PubDate	1986