Novel lymphocyte growth-inhibiting tripeptide: N-acetyl-glu-ser-GlyNH(2)

The limited and predetermined number of cells that constitutes an organ or specialized cell population is to all appearances regulated according to a negative feedback principle involving growth inhibitors with sufficient tis sue specificity. To find growth-inhibiting factors in lymphoid cells, we fo llowed established purification procedures and assays, We found a single-pe ak fraction in water extracts of dog spleen homogenates that inhibited prol iferation of Molt (T cell) lymphoma cells at low concentrations in vitro wi th no significant effect on a B cell lymphoma cell line (Ramos). C-terminal amino acid sequencing and MS analysis showed the factor to be a tripeptide : N-acetyl-Glu-Ser-GlyNH(2). Treatment with a synthetic tripeptide with the structure N-acetyl-Glu-Ser-GlyNH(2) decreased the number of cell doublings of Molt cells. The peptide also delayed cell flux at the G(2)-M transition of the cell cycle, while incorporation of tritiated thymidine was not alte red at the examined time points in this cell line. However, DNA synthesis i n PPD-stimulated normal human lymphocytes was significantly inhibited and w ith a bell-shaped dose-response curve. (C) 2000 Academic Press.