Structure-activity relationships of vasoactive peptides derived from fibrin or fibrinogen degraded by plasmin

The amino acid sequences of three vasoactive peptides which we previously isolated from fibrin(ogen) degraded by plasmin (EC 3.4.21.7) have been determined. Each peptide originates from a different chain of the fibrinogen molecule. Comparison with other studies shows that the two peptides having the permeability-increasing effect arise from regions of the fibrinogen' molecule that are easily accessible to plasmin attack. The third peptide, which has a slight vasoconstrictor activity, is part of fragment E released from the fibrinogen molecule after plasmin degradation. The two peptides having permeability-increasing effect lose their carboxyl-terminal lysine after interaction with carboxypeptidase B (EC 3.4.12.3) with a concomitant loss of activity. One of these peptides (6A) is resistant to tryptic digestion, while the second peptide (6D) is easily split into two inactive fragments. Complete deamination or modification of the free amino groups (carbamylation, methylation) almost completely abolishes their activity, whereas selective modification of only the free ϵ-amino groups of lysine does not. Modification of the Trp residue in one of these peptides (6D) increased its activity. These findings show that a carboxylterminal lysine with a free ϵ-amino group as well as an unblocked N-terminal residue are essential for their activity. Proline, which is situated near or at the middle of both peptides, is also apparently essential indicating that a specific conformation might be required for physiological activity.