ABSTRACT
Tuftsin, T-K-P-R, is a phagocytosis-stimulating peptide described as a natural immunostimulant. Four analogues of this peptide were synthesized. These compounds were assayed for their ability to compete with [3H]tuftsin for its specific receptor from thioglycollate-elicited mouse peritoneal macrophages. They were also tested for their ability to change level in intracellular cGMP and to stimulate phagocytosis through the nitroblue tetrazolium reduction measurement. Surprisingly, all the analogues were poor competitors of [3H]tuftsin binding but possess potent tuftsin-like activities.
Subject(s)
Macrophages/drug effects , Tuftsin/pharmacology , Amino Acid Sequence , Animals , Cyclic GMP/metabolism , Macrophages/metabolism , Male , Mice , Mice, Inbred Strains , Molecular Sequence Data , Phagocytosis/drug effects , Structure-Activity Relationship , Tuftsin/analogs & derivatives , Tuftsin/chemical synthesisABSTRACT
L1210 cells treated for 21 hours with S12363, a new vinca alkaloid derivative and the parent compounds (vinblastine, vincristine, vindesine) at equitoxic concentrations were found, by flow cytometry, to be equally accumulated in the G2 + M phase of the cell cycle. The chromatin structure of these cells was then analyzed in order to quantify with high precision the percentage of cells in mitosis. S12363 was found to accumulate, from the first hours of treatment (4-8 hours), and at lower concentrations, a higher percentage of cells in the M phase than the reference drugs. Taking into account previously published studies concerning the characteristics of vinblastine and vincristine uptake, our results are compatible with a facilitated uptake of S12363.
