Synthesis and biological activity of [L-3,4-dehydroproline3]-tuftsin

A 3,4-dehydroproline analogue of tuftsin (L-Thr-L-Lys-L-Pro-L-Arg) was prepared by the solid phase synthetic method. Following reversed-phase high performance liquid chromatography (HPLC) purification, the analogue was compared to tuftsin for its ability to to enhance the chemotactic, bactericidal and phagocytic activities of polymorphonuclear leukocytes (PMN). Both tuftsin and [delta 3-pro3]- tuftsin elicited a similar significant chemotactic effect at a concentration of 10 micrograms/ml. A slight suppression of the chemotactic activity was observed with tuftsin at 10(-3) micrograms/ml and with [delta 3-pro3]-tuftsin at concentrations of 10(-3), 10(-2) (significant) and 10-1 micrograms/ml. Although similar bactericidal activities were observed for both peptides, PMN exposed to [delta 3-pro 3]-tuftsin exhibited increased phagocytic indicies 2-4 times that of tuftsin-treated PMN at concentrations of 0.4, 0.6 and 1.0 microgram/ml.