The sequence A alpha-(154-159) of fibrinogen is capable of accelerating the t-PA catalysed activation of plasminogen.
The rate of activation of plasminogen by tissue-type plasminogen activator (t-PA) is greatly increased by fibrin, but much less by fibrinogen. Fibrin(ogen) fragments such as the fibrin(ogen) cyanogen bromide fragment FCB-2 and FCB-5, and a synthetic peptide with the sequence of fibrinogen A alpha-(148-160), a constituent of FCB-2, also have rate-enhancing properties. In order to find a possibly smaller, still stimulating site within A alpha-(148-160) we synthesized successive linear amino-terminally acylated hexapeptides [i.e. A alpha-(148-153), A alpha-(149-154)'d, .... A alpha-(155-160)] from the sequence A alpha-(148-160). The only hexapeptide within the sequence A alpha-(148-160) capable of enhancing the rate of plasminogen-to-plasmin conversion by t-PA appears to be the amino-terminally acylated peptide comprising the sequence A alpha-(154-159). This peptide enhances the plasminogen activation rate six-fold; half-maximal activation rate is reached at a peptide concentration of 56 microM.
Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands.
W J
WJ
Schielen
H P
HP
Adams
M
M
Voskuilen
G I
GI
Tesser
W
W
Nieuwenhuizen
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D005340:Fibrinogen / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator