Biomaterial Database

The interaction of disagregin with the platelet fibrinogen receptor, glycoprotein IIb-IIIa. 1997

J Karczewski, and T M Connolly

Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. jerzy-karczewski@merck.com

Disagregin, a 6 kDa protein isolated from salivary glands of the tick Ornithodoros Moubata, is a potent and selective inhibitor of fibrinogen dependent platelet aggregation and of the adhesion of platelets to fibrinogen (Karczewski et al. (1994) J. Biol. Chem. 269, 6702-6708). In the current study the interaction of disagregin with purified glycoprotein IIb-IIIa (GPIIb-IIIa) was examined. Biotin-labeled disagregin (b-disagregin) bound to GPIIb-IIIa immobilized on the surface of the ELISA plate. This binding was specific, dependent on divalent cations, and was blocked by the peptides fibrinogen gamma-chain fg gamma (400-411), GPIIb(296-306) and by the RGD-containing peptide, GRGDSP. Disagregin also bound to soluble GPIIb-IIIa as demonstrated in studies using the chemical crosslinker, BS3. This binding was inhibited by the peptides fg gamma (400-411) and GPIIb(296-306). In contrast to the results in the solid phase, peptide GRGDSP had no effect on the binding of b-disagregin to soluble GPIIb-IIIa. These data demonstrate that disagregin binds to GPIIb-IIIa through a mechanism distinct from that used by RGD-containing disintegrins. Further analysis of the region(s) of disagregin which bind to GPIIb-IIIa should provide useful information for molecular modeling of the fibrinogen binding site on GPIIb-IIIa and for the design of a new class of potent fibrinogen receptor antagonists.

UI	MeSH Term	Description	Entries
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D003432	Cross-Linking Reagents	Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.	Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D012471	Salivary Proteins and Peptides	Proteins and peptides found in SALIVA and the SALIVARY GLANDS. Some salivary proteins such as ALPHA-AMYLASES are enzymes, but their composition varies in different individuals.	Salivary Gland Protein,Salivary Gland Proteins,Salivary Peptide,Salivary Protein,Salivary Proteins,Salivary Peptides,Gland Protein, Salivary,Peptide, Salivary,Protein, Salivary,Protein, Salivary Gland
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D013987	Ticks	Blood-sucking acarid parasites of the order Ixodida comprising two families: the softbacked ticks (ARGASIDAE) and hardbacked ticks (IXODIDAE). Ticks are larger than their relatives, the MITES. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many TICK-BORNE DISEASES, including the transmission of ROCKY MOUNTAIN SPOTTED FEVER; TULAREMIA; BABESIOSIS; AFRICAN SWINE FEVER; and RELAPSING FEVER. (From Barnes, Invertebrate Zoology, 5th ed, pp543-44)	Ixodida,Ixodidas,Tick
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019039	Platelet Glycoprotein GPIIb-IIIa Complex	Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.	GPIIb-IIIa Receptors,Integrin alphaIIbbeta3,Glycoproteins IIb-IIIa,Integrin alpha-IIb beta-3,GPIIb IIIa Receptors,Glycoproteins IIb IIIa,Integrin alpha IIb beta 3,Platelet Glycoprotein GPIIb IIIa Complex,Receptors, GPIIb-IIIa,alphaIIbbeta3, Integrin,beta-3, Integrin alpha-IIb