Anticoagulant and antithrombotic properties of a γ-carboxyglutamic acid-rich peptide derived from the light chain of blood coagulation factor X

Peter P. Nawroth, Walter Kisiel, David Stern

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Abstract

In this report, we describe the anticoagulant and antithrombotic properties of a peptide (residues 1-44) derived from the amino-terminus of the bovine Factor X light chain by limited proteolysis with chymotrypsin, and subsequently purified by QAE-Sephadex chromatography. The effect of Factor X gla-peptide on the activation of human 3H-Factors IX and X was studied using radiometric assays and purified coagulation factors. Factor VIIa-tissue factor catalyzed activation of Factors IX and X was half-maximally inhibited by Factor X gla-peptide at concentrations of 0.8 μM and 0.2 μM, respectively. Factor IXa-VIII catalyzed Factor X activation was half-maximally inhibited at a gla-peptide concentration of 0.5 μM. In addition, thrombin formation by platelets incubated with Factor Xa and prothrombin could be similarly blocked by gla-peptide. Studies with bovine aortic endothelial cells indicated that the Factor X gla-peptide blocked in parallel Factor X binding and activation on the cell surface. Decarboxylation of the peptide by acid heat treatment destroyed its anticoagulant activity. The in vivo anticoagulant potential of native gla-peptide was demonstrated by a rapid prolongation of the PT and APTT following intravenous infusion into a rabbit. In addition, gla-peptide prevented thrombus formation in response to Factors IXa and Xa, but not thrombin, in a Wessler venous stasis model.

Original languageEnglish (US)
Pages (from-to)625-637
Number of pages13
JournalThrombosis Research
Volume44
Issue number5
DOIs
StatePublished - Dec 1 1986

Fingerprint

Factor X
Anticoagulants
Light
Peptides
Acids
Factor IXa
Factor Xa
Factor IX
Thrombin
Factor VIIa
Decarboxylation
Blood Coagulation Factors
Factor VIII
Chymotrypsin
Thromboplastin
Prothrombin
Intravenous Infusions
Proteolysis
Chromatography
Thrombosis

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Anticoagulant and antithrombotic properties of a γ-carboxyglutamic acid-rich peptide derived from the light chain of blood coagulation factor X. / Nawroth, Peter P.; Kisiel, Walter; Stern, David.

In: Thrombosis Research, Vol. 44, No. 5, 01.12.1986, p. 625-637.

Research output: Contribution to journalArticle

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