FVIIa derivatives obtained by autolytic and controlled cathepsin G mediated cleavage

Abstract

The heavy chain of coagulation factor VII contains a serine esterase entity. A partial cleavage in the heavy chain occurs during purification and activation of the single‐chain zymogen, presumably as a result of autolysis. Neutrophil cathepsin G initially generates a Gla‐domainless FVIIa without coagulant activity. However, on extended exposure cleavage also occurs in the heavy chain, resulting in a complete loss of enzyme activity. Four cleavage sites on the heavy chain, two susceptible to trypsin‐like autolysis and two susceptible to chymotrypsin‐like cathepsin G‐mediated catalysis have been identified. The hydrolysis of peptide bonds in the heavy chain might contribute to regulation of the coagulation process in vivo.

Mass spectrometric characterization of N- and O-glycans of plasma-derived coagulation factor VII

“…The other peaks originate from hydrolysis of HC either after Arg 290 or Arg 315 as deduced from accurate mass measurement (Table 1). These observations are also corroborated by previous data [29].…”

Characterization of canine coagulation factor VII and its complex formation with tissue factor: canine–human cross‐species compatibility

“…Trace amounts of degradation products and activated enzyme were present in the preparation. cFVIIa degradation products were shown by N‐terminal sequencing to originate from cleavage in the Gla domain and in the protease domain at positions essentially equivalent to those obtained by autodegradation of hFVIIa [41].…”

Successful treatment of canine hemophilia by continuous expression of canine FVIIa

“…The lower molecular weight bands observed at 10 to 16 kDa are probably degradation products, as have been previously observed in human recombinant FVIIa preparations. 23,24 Although the heavy and light chains of cFVIIa exhibited differential staining with Coomassie blue, this is commonly found in human 23,24 as well as murine FVIIa preparations. 9 For personal use only.…”