ENHANCED PHAGOCYTOSIS ACTIVITY OF CYCLIC ANALOGS OF TUFTSIN

Cyclic analogs of the physiological immunostimulating peptide tuftsin (Thr-Lys-Pro-Arg), cyclo(Thr-Lys-Pro-Arg-Gly) (ctuf-G) and cyclo(Tnr-L ys-Pro-Arg-Asp) (ctuf-D), were synthesized based on molecular modeling studies, and assayed for the ability to stimulate phagocytosis by hum an polymorphonuclear leukocytes. As predicted, the synthesis of ctuf-D resulted in two isomers with the correct molecular mass and amino aci d composition. In phagocytosis assays, tuftsin, ctuf-G and two isomers of ctuf-D showed the usual bell-shaped activity profiles. The optimum concentration of ctuf-G was 50-fold less than that of tuftsin, wherea s the degree of stimulation was similar. One isomer of ctuf-D was almo st inactive, and the other ctuf-D exhibited the same degree of phagocy tosis as tuftsin but its optimum concentration was 5-fold lower. The e nhanced potency of ctuf-G and one isomer of ctuf-D may be due to confo rmational effects and/or to the possibility that these cyclic peptides are resistant to proteolytic degradation.