Fibrinogen Bergamo I (Aα16Arg → Cys): Susceptibility Towards Thrombin Following Aminoethylation, Methylation or Carboxamidomethylation of Cysteine Residues

P Reber; M Furlan; E A Beck; G Finazzi; M Buelli; T Barbui

doi:10.1055/s-0038-1657746

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1985; 54(02): 390-393
DOI: 10.1055/s-0038-1657746

Original Article

Schattauer GmbH Stuttgart

Fibrinogen Bergamo I (Aα16Arg → Cys): Susceptibility Towards Thrombin Following Aminoethylation, Methylation or Carboxamidomethylation of Cysteine Residues

P Reber

¹The Central Hematology Laboratory, Inselspital, Bern, Switzerland

,

M Furlan

¹The Central Hematology Laboratory, Inselspital, Bern, Switzerland

,

E A Beck

¹The Central Hematology Laboratory, Inselspital, Bern, Switzerland

,

G Finazzi

²The Istituto di Ricerche Farmacologiche “Mario Negri”, Bergamo, Italy

,

M Buelli

³The Divisione di Ematologia, Ospedali Riuniti di Bergamo, Italy

,

T Barbui

³The Divisione di Ematologia, Ospedali Riuniti di Bergamo, Italy

› Author Affiliations

Abstract

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Summary

An abnormal fibrinogen, denoted as “fibrinogen Bergamo I”, has been characterized. Its defect consists in an exchange of arginine by cysteine in position 16 of the Aα-chain, thus corresponding to that found in a number of other fibrinogen variants. The abnormal fibrinopeptide A cannot be split off by thrombin from intact fibrinogen Bergamo I. We describe three different chemical modifications of the cysteine Aαl6, i.e. aminoethylation, methylation and carboxamidomethylation, and their effects on the susceptibility of fibrinogen Bergamo I towards thrombin attack. S-aminoethylation of the Aαl6Cys renders the peptide bond Aαl6–17 cleavable by thrombin. Following methylation or carboxamidomethylation, the Aαl9-arginyl bond becomes accessible for thrombin. The chemically modified extended fibrinopeptide A can be readily separated from the normal fibrinopeptide A by HPLC. The latter two modifications are suitable alternative procedures for detecting the molecular defect Aαl6Arg → Cys of fibrinogen.

Keywords

Dysfibrinogenemia - Fibrinogen Bergamo I

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References

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