"Bridged" peptide of fibrinogen binds to platelets activated by RGD peptide as well as by ADP. 1994

H Mohri, and T Ohkubo
First Department of Internal Medicine, Yokohama City University, School of Medicine, Japan.

We have evaluated the binding of a bridged peptide of Y-HHLGGAKQAGDV(G)9RGDS to RGDS-activated platelets. The bridged peptide saturably bound to platelets activated by RGDS peptide and by ADP with binding sites of 38,600 +/- 4800 molecules/platelet (Kd = 8.9 +/- 1.3 x 10(-7) M) and 43,600 +/- 9,200 molecules/platelet (Kd = 3.1 +/- 0.5 x 10(-7) M), respectively. Native fibrinogen inhibited the binding of the bridged peptide to platelets activated by RGDS peptide and by ADP with IC50s of 1.2 +/- 0.4 microM and 1.8 +/- 0.6 microM, respectively. In addition, the RGDS peptide and the dodecapeptide (gamma 400-411; HHLGGAKQAGDV) completely inhibited the binding of the bridged peptide to platelets activated by RGDS peptide with IC50s of 32 +/- 2.6 microM for RGDS and 102 +/- 4.1 microM for gamma 400-411, respectively. The anti-GPIIb/IIIa monoclonal antibody, LJ-CP8, also inhibited these bindings. The IC50s were 75 +/- 8.6 micrograms/ml for RGDS activation and 56 +/- 6.3 micrograms/ml for ADP stimulation. These results suggest that the flexible hinge region may allow assumption of the appropriate structure in the presence of the receptor complex. It indicates that both RGDS and agonist stimulation may play an important role in inducing activation of platelets that results in further platelet aggregation and tight thrombus formation.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
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
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
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
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
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
D005069 Evaluation Studies as Topic Works about studies that determine the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. Critique,Evaluation Indexes,Evaluation Methodology,Evaluation Report,Evaluation Research,Methodology, Evaluation,Pre-Post Tests,Qualitative Evaluation,Quantitative Evaluation,Theoretical Effectiveness,Use-Effectiveness,Critiques,Effectiveness, Theoretical,Evaluation Methodologies,Evaluation Reports,Evaluation, Qualitative,Evaluation, Quantitative,Evaluations, Qualitative,Evaluations, Quantitative,Indexes, Evaluation,Methodologies, Evaluation,Pre Post Tests,Pre-Post Test,Qualitative Evaluations,Quantitative Evaluations,Report, Evaluation,Reports, Evaluation,Research, Evaluation,Test, Pre-Post,Tests, Pre-Post,Use Effectiveness
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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