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 - DFBPANTH0003(Antithrombotic peptide)

DFBP ID	DFBPANTH0003
Peptide sequence	KRDS
Type	Native peptide
Peptide/Function name	Antithrombotic peptide

Function-activity relationship

Main bioactivity	Antithrombotic activity
Otheir bioactivity	N.D

Calculated physicochemical properties

Three-letter amino acid

Lys-Arg-Asp-Ser

Single-letter amino acid

KRDS

Peptide length

Peptide mass

Experimental mass	Theoretical mass
N.D	504.53 Da ^c

Net charge

0.00 ^c

Isoelectric point (pI)

10.04 ^c

IC₅₀

N.D

pIC₅₀

N.D

GRAVY

-3.1750^c

Hydrophilic residue ratio

0%^c

Peptide calculator

Peptide source & Food-borne protein(s) search

Classification	Human
Organism/Source	Human milk protein
Precursor protein	Lactotransferrin
Residue position	f(39-42)
Precursor protein(s) search	Source.1: DFBPPR0810 ---- Plant proteins ---- APETALA2-like protein 1 Source.2: DFBPPR0812 ---- Plant proteins ---- ATP-dependent DNA helicase MER3 homolog Source.3: DFBPPR1319 ---- Plant proteins ---- Calcium-dependent protein kinase 17 Source.4: DFBPPR1407 ---- Plant proteins ---- Indole-3-acetate O-methyltransferase 1 Source.5: DFBPPR2284 ---- Plant proteins ---- Probable glucan 1,3-alpha-glucosidase Source.6: DFBPPR2504 ---- Plant proteins ---- 14-3-3-like protein GF14-B Source.7: DFBPPR2828 ---- Plant proteins ---- ABC transporter G family member 36 Source.8: DFBPPR3175 ---- Plant proteins ---- Kinesin-like protein KIN-7I Source.9: DFBPPR3844 ---- Plant proteins ---- Probable protein phosphatase 2C 41 Source.10: DFBPPR4426 ---- Plant proteins ---- Protein argonaute 18 Source.11: DFBPPR4681 ---- Plant proteins ---- Acidic leucine-rich nuclear phosphoprotein 32-related protein 2 Source.12: DFBPPR5855 ---- Plant proteins ---- 14-3-3-like protein GF14-6 Source.13: DFBPPR7596 ---- Milk proteins ---- Lactotransferrin Source.14: DFBPPR16012 ---- Animal proteins ---- Mast/stem cell growth factor receptor Kit Source.15: DFBPPR16055 ---- Animal proteins ---- Glutamate receptor ionotropic, NMDA 2B Source.16: DFBPPR16693 ---- Animal proteins ---- Cingulin Source.17: DFBPPR16760 ---- Animal proteins ---- Carnitine O-acetyltransferase Source.18: DFBPPR17019 ---- Animal proteins ---- Mast/stem cell growth factor receptor Kit Source.19: DFBPPR18073 ---- Animal proteins ---- Endoplasmic reticulum aminopeptidase 2 Source.20: DFBPPR18143 ---- Animal proteins ---- NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 Source.21: DFBPPR18167 ---- Animal proteins ---- Ubiquitin thioesterase ZRANB1 Source.22: DFBPPR18306 ---- Animal proteins ---- Serine/threonine-protein kinase 10 Source.23: DFBPPR19119 ---- Animal proteins ---- Phospholipase D2 Source.24: DFBPPR19227 ---- Animal proteins ---- Nuclear speckle splicing regulatory protein 1 Source.25: DFBPPR19253 ---- Animal proteins ---- Limbin Source.26: DFBPPR19346 ---- Animal proteins ---- Cylicin-1 Source.27: DFBPPR19382 ---- Animal proteins ---- Arrestin-C Source.28: DFBPPR19507 ---- Animal proteins ---- Glutathione synthetase Source.29: DFBPPR20196 ---- Animal proteins ---- Mediator of RNA polymerase II transcription subunit 4 Source.30: DFBPPR20435 ---- Animal proteins ---- Leucine-rich glioma-inactivated protein 1 Source.31: DFBPPR20625 ---- Animal proteins ---- DIS3-like exonuclease 1 Source.32: DFBPPR20983 ---- Animal proteins ---- Plakophilin-3 Source.33: DFBPPR21024 ---- Animal proteins ---- Glycosylated lysosomal membrane protein Source.34: DFBPPR21401 ---- Animal proteins ---- THAP domain-containing protein 5 Source.35: DFBPPR21480 ---- Animal proteins ---- WD repeat and FYVE domain-containing protein 1 Source.36: DFBPPR21566 ---- Animal proteins ---- Phosducin-like protein 3 Source.37: DFBPPR8550 ---- Animal proteins ---- Complement C3 Source.38: DFBPPR8695 ---- Animal proteins ---- Mast/stem cell growth factor receptor Kit Source.39: DFBPPR9599 ---- Animal proteins ---- Biogenesis of lysosome-related organelles complex 1 subunit 5 Source.40: DFBPPR9813 ---- Animal proteins ---- Secreted phosphoprotein 24 Source.41: DFBPPR10075 ---- Animal proteins ---- Mast/stem cell growth factor receptor Kit Source.42: DFBPPR10212 ---- Animal proteins ---- Gamma-aminobutyric acid receptor subunit gamma-4 Source.43: DFBPPR10257 ---- Animal proteins ---- Inner centromere protein Source.44: DFBPPR10363 ---- Animal proteins ---- E3 ubiquitin-protein ligase HACE1 Source.45: DFBPPR10384 ---- Animal proteins ---- Myosin-binding protein C, cardiac-type Source.46: DFBPPR10876 ---- Animal proteins ---- Telomere-associated protein RIF1 Source.47: DFBPPR10940 ---- Animal proteins ---- Protein piccolo Source.48: DFBPPR10964 ---- Animal proteins ---- Protein artemis Source.49: DFBPPR11274 ---- Animal proteins ---- Muscarinic acetylcholine receptor M3 Source.50: DFBPPR11495 ---- Animal proteins ---- Calretinin Source.51: DFBPPR11511 ---- Animal proteins ---- E3 ubiquitin-protein ligase MIB2 Source.52: DFBPPR11534 ---- Animal proteins ---- Coiled-coil domain-containing protein 80 Source.53: DFBPPR11925 ---- Animal proteins ---- GSK3-beta interaction protein Source.54: DFBPPR12068 ---- Animal proteins ---- Serine/arginine repetitive matrix protein 1 Source.55: DFBPPR12069 ---- Animal proteins ---- Transmembrane channel-like protein 7 Source.56: DFBPPR12781 ---- Animal proteins ---- Melanotransferrin Source.57: DFBPPR13238 ---- Animal proteins ---- Laminin subunit gamma-2 Source.58: DFBPPR13427 ---- Animal proteins ---- Mast/stem cell growth factor receptor Kit Source.59: DFBPPR13716 ---- Animal proteins ---- Trichohyalin Source.60: DFBPPR14421 ---- Marine protein ---- Protein translocase subunit SecA Source.61: DFBPPR14891 ---- Microorganism protein ---- DNA polymerase epsilon catalytic subunit A Source.62: DFBPPR15002 ---- Microorganism protein ---- Dihydroorotate dehydrogenase (quinone), mitochondrial Source.63: DFBPPR15014 ---- Microorganism protein ---- AP-1-like transcription factor YAP1 Source.64: DFBPPR15055 ---- Microorganism protein ---- DNA damage-inducible protein 1 Source.65: DFBPPR15115 ---- Microorganism protein ---- Helicase SWR1 Source.66: DFBPPR15397 ---- Microorganism protein ---- Nucleolar GTP-binding protein 2 Source.67: DFBPPR15662 ---- Microorganism protein ---- Nuclear rim protein 1 Source.68: DFBPPR15685 ---- Microorganism protein ---- Zinc-regulated protein 8
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

(1) KRDS inhibited ADP-induced platelet aggregation [median inhibitory concentration (1C₅₀) 350 μM] and fibrinogen binding (1C₅₀ 360 μM) to a lesser extent than RGDS (1C₅₀75 μM and 20 μM, respectively). Different from RGDS, thrombin-induced serotonin release was inhibited by KRDS (750 μM) on normal platelets (55 ± 10%) and type I Glanzmann’s thrombasthenia platelets (43% ± 1). However, KRDS had no effect on cytoplasmic Ca²⁺ mobilization, inositol phospholipid metabolism or protein phosphorylation (myosin light chain P20 and P43). In contrast to RGDS, KRDS does not inhibit the binding of monoclonal antibody PAC-1 to activated platelets. KRDS and RGDS inhibited 4β-phorbol-12-myristate-13-acetate (PMA)-induced aggregation and fibrinogen binding, while proteins were normally phosphorylated.
(2) The inhibition was demonstrated to be mediated by a mechanism which requires the binding of lactotransferrin to its putative receptor and not to platelet glycoprotein IIb-IIIa ^[5].

Specific target protein(s)

Potential Target Protein(s):
Integrin alpha-2
Platelet glycoprotein IX
Platelet glycoprotein Ib alpha chain
Platelet glycoprotein Ib beta chain
Platelet glycoprotein 4
Platelet glycoprotein 4

Taste properties & Structure

Bitterness

Literature report	N.D
Bitter prediction tools	Non-bitter taste ^prediction

SMILES

N[C@@]([H])(CCCCN)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CC(=O)O)C(=O)N[C@@]([H])(CO)C(=O)O

Preparation method

Mode of preparation	Synthetic peptide
Enzyme(s)/starter culture	The synthetic peptides used throughout this study were prepared using a 430A peptide synthetizer (Applied Biosystems).

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

(1) The concentrations of both sheep or human lactoferrins required to obtain 100% and 50% (IC₅₀) inhibition of thrombin-induced aggregation were 25 or 25 μM and 5 or 4 μM, respectively ^[2].
(2) The peptide showed inhibition on binding of monoclonal antibodies to platelet glycoproteins (GPIIb-GPIIIa)^[4].

Database cross-references

[D1]

[D2]

[D3]

[D4]

Reference(s)

Primary literature	Mazoyer E, Lévy-Toledano S, Rendu F, Hermant L, Lu H, Fiat AM, Jollès P, Caen J. KRDS, a new peptide derived from human lactotransferrin, inhibits platelet aggregation and release reaction. Eur J Biochem. 1990 Nov 26;194(1):43-9. PMID: 2174781 DOI: 10.1111/j.1432-1033.1990.tb19424.x
Other literature(s)	[1] Park Y W. Bioactive Components in Milk and Dairy Products[M]. 2009. [2] Qian Z Y, Jollès P, Migliore-Samour D, et al. Isolation and characterization of sheep lactoferrin, an inhibitor of platelet aggregation and comparison with human lactoferrin[J]. Biochimica Et Biophysica Acta General Subjects, 1995, 1243(1):25-32. [3] Meddeb S, Demaret J P, Ballini J P, et al. A conformational study of Lys-Arg-Asp-Ser and analogs, a series of potent antithrombotic peptides. An approach based on simulated annealing and 1H NMR.[J]. Journal of Biomolecular Structure & Dynamics, 1994, 11(5):959. [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] Leveugle B, Mazurier J, Legrand D, et al. Lactotransferrin binding to its platelet receptor inhibits platelet aggregation[J]. European Journal of Biochemistry, 1993, 213(3):1205-1211.
PubDate	1990