Biomaterial Database

Synthetic peptides demonstrate RGD-independent platelet glycoprotein IIb/IIIa recognition site in cell binding domain of human fibronectin. 1995

H Mohri, and J Tanabe, and K Katoh, and T Okubo

First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.

Fibronectin binds to platelet membrane glycoprotein (GP) IIb/IIIa in both an Arg-Gly-Asp (RGD)-dependent and -independent manner. The identification of an RGD-independent binding domain(s) that interacts with GPIIb/IIIa may be the key to understand the mechanism of thrombus formation. A recombinant fibronectin fragment containing the residues from Ile1359 to Ser1436 (lacking the RGD sequence) had been shown to bind to GPIIb/IIIa in a divalent cation- and activation-dependent manner. To identify a minimal peptide ligand that participates in the recognition of GPIIb/IIIa, we synthesized peptides extending this region, which consist of 12 amino acid residues in length and overlapping by six amino acids. We obtained evidence that two 12-residue peptide sequences from this region (residues 1371-1382 and 1377-1388) inhibit fibronectin binding to GPIIb/IIIa by interacting directly with this receptor, with IC50s of 95 +/- 16 and 104 +/- 19 microM, respectively. These peptides inhibited the binding of fibrinogen to GPIIb/IIIa, as well as ADP-induced platelet aggregation. These results indicate that an RGD-independent GPIIb/IIIa binding site in the cell binding domain of fibronectin was localized within the residues His1377-Ile1382.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010974	Platelet Aggregation	The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.	Aggregation, Platelet
D010980	Platelet Membrane Glycoproteins	Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.	PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
D001792	Blood Platelets	Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.	Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D005340	Fibrinogen	Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.	Coagulation Factor I,Factor I,Blood Coagulation Factor I,gamma-Fibrinogen,Factor I, Coagulation,gamma Fibrinogen
D005353	Fibronectins	Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.	Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000244	Adenosine Diphosphate	Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.	ADP,Adenosine Pyrophosphate,Magnesium ADP,MgADP,Adenosine 5'-Pyrophosphate,5'-Pyrophosphate, Adenosine,ADP, Magnesium,Adenosine 5' Pyrophosphate,Diphosphate, Adenosine,Pyrophosphate, Adenosine