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(Thr-Lys-Pro-Arg-Asp) (ctuf-D), were synthesized based on molecular modeling studies, and assayed for the ability to stimulate phagocytosis by human polymorphonuclear leukocytes. As predicted, the synthesis of ctuf-D resulted in two isomers with the correct molecular mass and amino acid 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, whereas the degree of stimulation was similar. One isomer of ctuf-D was almost inactive, and the other ctuf-D exhibited the same degree of phagocytosis as tuftsin but its optimum concentration was 5-fold lower. The enhanced potency of ctuf-G and one isomer of ctuf-D may be due to conformational effects and/or to the possibility that these cyclic peptides are resistant to proteolytic degradation.
Nishioka
K
K
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.
Obeyesekere
N U
NU
McMurray
J S
JS
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D010456:Peptides, Cyclic; D014405:Tuftsin