TAN-1511-A, TAN-1511-B AND TAN-1511-C, MICROBIAL LIPOPEPTIDES WITH G-CSF AND GM-CSF INDUCING ACTIVITY

The microbial lipopeptides, TAN-1511 A, B and C, were isolated from th e culture broth of streptosporangium amethystogenes subsp. fukuiense A L-23456. Their structures were elucidated on the basis of their reacti ons and spectroscopic analyses. These lipopeptides were mixtures of mo lecules having different lengths of fatty acids. The metabolites stimu lated the proliferation of bone marrow cells from BALB/c female mice a t very low concentrations (concentration giving 30% increase: A and B, 0.313 ng/ml; C, 1.25 ng/ml). We confirmed that chemically synthesized TAN-1511 A analogue yloxy)-4-thiaheptanoyl-Gly-Gly-Gly-Glu-Thr-Thr-OH ] stimulated the proliferation of bone marrow cells in a manner simila r to that of natural TAN-1511 A. This analogue induced the secretion o f both granulocyte colony stimulating factor (G-CSF) and granulocyte-m acrophage colony stimulating factor (GM-CSF), and potentiated the gene ration of Gr-1 positive cells in the bone marrow cell culture. Moreove r, it effected the G-CSF mediated restoration of granulocytopoiesis in a murine leukopenia model.