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January 1, 2001Thrombosis and Haemostasis

Identification of Critical Residues on Thrombin Mediating Its Interaction with Fibrin

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Key result

Four residues (Lys65, His66, Tyr71, Arg73) within exosite I mediate fibrin binding, and a DNA thrombin aptamer targeting these residues successfully inhibited the thrombin-fibrin interaction.

Population

52 purified thrombin mutants

Design

Preclinical

Authors

SHS W HallUniversity of ReadingCGCraig S. GibbsAtara Biotherapeutics (United States)LLLawrence LeungAlbert Einstein College of Medicine

Discussion

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Implication

Exosite I-targeted aptamers merit further preclinical testing; leaves open clinical antithrombotic translation.

Structured PICO

P
Population
In vitro study using 52 purified thrombin mutants to identify residues mediating thrombin-fibrin interaction.
I
Intervention
Mutagenesis and application of a DNA thrombin aptamer
O
Outcome
Fibrinogen clotting activity and fibrin binding activitysurrogate

Four specific residues within exosite I of thrombin mediate its interaction with fibrin, an interaction that can be inhibited by a targeted DNA aptamer.

Cite This Study

Hall et al. (2001) studied this question. Thrombin mutants and DNA thrombin aptamer was evaluated on Fibrinogen clotting activity and fibrin binding activity. Four residues (Lys65, His66, Tyr71, Arg73) within exosite I mediate fibrin binding, and a DNA thrombin aptamer targeting these residues successfully inhibited the thrombin-fibrin interaction.

synapsesocial.com/papers/6a218e68b92297459dab87dbhttps://doi.org/10.1055/s-0037-1616750
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Binding of <i>α</i>-thrombin to fibrin depends on the quality of the fibrin network1994 · 30 citations
  2. 2A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation1994 · 108 citations
  3. 3Fibrinogen Milano II: A Congenital Dysfibrinogenaemia Associated with Juvenile Arterial and Venous Thrombosis1986 · 36 citations
  4. 4Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis1989 · 117 citations
  5. 5Binding of Fibrin Monomer and Heparin to Thrombin in a Ternary Complex Alters the Environment of the Thrombin Catalytic Site, Reduces Affinity for Hirudin, and Inhibits Cleavage of Fibrinogen1996 · 53 citations