Studies on hybrid peptides of fragments from fibrinogen

In the present paper the hybrid peptides of P6A and RGD, namely ARPAKRGDS 17, ARPAKRGDV 19, ARPAKRGDF 21, QRPAKRGDS 18, QRPAKRGDV 20 and QRPAKRGDF 22, were synthesized via the solution method, segment condensation and TFA/TFMSA-catalyzed deprotection (in 93–96% yield). The bioassay indicated that all of the tetrapeptides, pentapeptides and nonapeptides showed vasodilating effect obviously. Coupling tetrapeptides with pentapeptides gave no significant advantageous to enhancing the vascular activity. Antiaggregation effect in vitro suggested the tetrapeptides and pentapeptides were more sensitive to ADP than PAF. The hybrid peptides, however, were sensitive to both of the two aggregators, suggested the antiaggregation effect may be enhanced by use of this hybrid strategy. Antithrombosis effect in vivo showed that coupling RGDS 14 and RGDV 15 with pentapeptides may improve the bioactivity. If RGDF 16 was used instead of RGDS and RGDV the coupling gave negative results. The bioactivity mentioned may be understood with the help of the energies of their stable conformations.