Fibrinogen Bergamo I (A alpha 16Arg----Cys): susceptibility towards thrombin following aminoethylation, methylation or carboxamidomethylation of cysteine residues

Abstract

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 A alpha-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 A alpha 16, i.e. aminoethylation, methylation and carboxamidomethylation, and their effects on the susceptibility of fibrinogen Bergamo I towards thrombin attack. S-aminoethylation of the A alpha 16Cys renders the peptide bond A alpha 16-17 cleavable by thrombin. Following methylation or carboxamidomethylation, the A alpha 19-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 A alpha 16Arg----Cys of fibrinogen.