Synthesis and Thrombolytic Activity of Pseudopeptides Related to Fibrinogen Fragment

Two kinds of linkers consisting of 3-(S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, ARPAK, GRPAK and QRPAK were synthesized. The thrombolytic activities in vivo indicated that the coupling position of 3-(S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid in the peptides effected on the potencies significantly. When the C-terminal of the peptides was amidated by 3-(S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, the thrombolytic potency of the peptides was enhanced or kept. When the N-terminal of the peptides was acylated by 3-(S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, however, the thrombolytic effect of the peptides was banished. The expected specific β II′-turn conformation and the stability to trypsin in the pseudopeptides with 3-(S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid in its C-terminal may be responsible for the enhanced thrombolytic potency.