Functional and Sequence Characterization of Agkicetin, a New Glycoprotein IB Antagonist Isolated from Agkistrodon acutus Venom

Chen, Yuh Ling; Tsai, Inn-Ho

doi:10.1006/bbrc.1995.1684

Cited by 55 publications

(23 citation statements)

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“…These include echicetin, 9 jararaca GPIb-binding protein, 10,11 tokaracetin, 12 CHH-A and -B, 4 and agkicetin. 13 Echicetin, a heterodimeric snake C-type lectin from Echis carinatus, has been shown by several authors to bind specifically to platelet GPIb and to block platelet interactions with von Willebrand factor (vWf) 9 and with thrombin. 14 There has been considerable interest in using C-type lectins, such as echicetin as antithrombotics, in blocking the interaction between vWf and platelets.…”

Section: Introductionmentioning

confidence: 99%

Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction

Navdaev

Dörmann

Clemetson

et al. 2001

Blood

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Section: Introductionmentioning

confidence: 99%

Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction

Navdaev

Dörmann

Clemetson

et al. 2001

Blood

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“…Anfibatide (also named agkicetin), a protein derived from the venom of Agkistrodon acutus , 24 is another potent platelet GPIb antagonist. 25 Anfibatide is a ~30-kDa protein comprising 2 mature subunits (~15 and ~14 kDa) that are linked by a disulfide bond.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura

et al. 2016

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Thrombotic thrombocytopenic purpura (TTP), a potentially fatal blood clot disorder, is primarily caused by severe deficiency of plasma ADAMTS13 activity resulting from acquired autoantibodies. Plasma exchange is the only effective initial therapy. However, the high mortality rate and the complications associated with plasma exchange therapy remain a major concern. To address unmet clinical needs, therapeutic efficacies of anfibatide, a snake venom-derived platelet glycoprotein Ib antagonist, in murine models of spontaneous thrombocytopenia and shigatoxin-induced TTP were determined. A light scattering platelet aggregometry, microfluidic shear-based assay, and murine models of TTP were used in the study. We showed that purified anfibatide inhibits ristocetin- or botrocetin-induced human or murine platelet agglutination in the presence of von Willebrand factor in a concentration-dependent manner. Anfibatide could also dramatically inhibit the adhesion and aggregation of murine and human platelets on a collagen surface under arterial shear stress, in the presence or absence of plasma ADAMTS13 activity. Most importantly, we demonstrated that an intraperitoneal administration of anfibatide at the dose of 60 ng/g body weight twice daily mitigated spontaneous thrombocytopenia and prevented shigatoxin-induced TTP in Adamts13−/− and disease-susceptible mice (CAST/Ei strain). Thus, we conclude that anfibatide, when administered at the optimal dosage, route, and interval, is efficacious in treating spontaneous and bacterial shigatoxin-induced TTP in the murine models. Our findings may provide the basis for further development of anfibatide for the treatment of acute TTP in humans.

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“…ACFI is an anticoagulant C-type lectin-like protein that consists of two subunits and heterodimerization of these is required for its function (32). Agkicetin -obtained from the venom of the Taiwanese Agkistrodon acutus -is a disulfide-linked heterodimer that comprises subunits of 15 and 14 kDa (33). It behaved as a potent antagonist of von Willebrand factorinduced platelet agglutination and bound specifically to GPIb of fixed platelets with high affinity.…”

Section: +mentioning

confidence: 99%

Acutolysin C, a weak hemorrhagic toxin from the venom of Agkistrodon acutus with leucoagglutination activity

Wei¹,

Chen²,

Jh³

2011

J. Venom. Anim. Toxins incl. Trop. Dis

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Abstract:The properties and agglutination activity of acutolysin C, a hemorrhagic metalloproteinase obtained from Agkistrodon acutus venom, were studied herein. Acutolysin C is a basic glycoprotein consisting of a single polypeptide chain with a molecular weight of 23.1 kDa and pI 8.7, containing one Zn 2+ and one Ca 2 + per molecule. It possesses caseinolytic, weak lethal (LD 50 = 7.6 mg/kg) and weak hemorrhagic (MHD = 12.0 μg) activities, but does not present fibrinolytic, fibrinogenolytic, arginine esterase and phospholipase A 2 actions. In addition, it revealed agglutination activity on some animal lymphocytes, including five species of mammals, six of birds, three of reptiles and one of amphibians, but had no effect on lymphocytes from two species of reptiles, one amphibian and nine species of fish. It had no effects on the erythrocytes and platelets of all 26 animal species tested. Both leucoagglutination and caseinolytic activities were inhibited by EDTA; while cysteine, 2-mercaptoethanol, 1,4-dithiothreitol, glutathione, serum against acutolysin C and serum against homologous snake venom as well as glucose, sucrose, mannose, lactose and galactose had no effects on inhibition. The lowest concentration of acutolysin C that induced mouse lymphocyte agglutination was 2.5 μg/mL. Acutolysin C is an interesting substance since it is the first member of the hemorrhagin family to be shown to have leucoagglutination activity.

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Functional and Sequence Characterization of Agkicetin, a New Glycoprotein IB Antagonist Isolated from Agkistrodon acutus Venom

Cited by 55 publications

References 0 publications

Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction

Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction

Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura

Acutolysin C, a weak hemorrhagic toxin from the venom of Agkistrodon acutus with leucoagglutination activity

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