TAN-1511 A, B and C, microbial lipopeptides with G-CSF and GM-CSF inducing activity.
The microbial lipopeptides, TAN-1511 A, B and C, were isolated from the culture broth of Streptosporangium amethystogenes subsp. fukuiense AL-23456. Their structures were elucidated on the basis of their reactions and spectroscopic analyses. These lipopeptides were mixtures of molecules having different lengths of fatty acids. The metabolites stimulated the proliferation of bone marrow cells from BALB/c female mice at 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 [(2R,6R)-2-tetradecanoylamino-6,7- bis(hexadecanoyloxy)-4-thiaheptanoyl-Gly-Gly-Gly-Glu-Thr-Thr -OH] stimulated the proliferation of bone marrow cells in a manner similar to that of natural TAN-1511 A. This analogue induced the secretion of both granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF), and potentiated the generation of Gr-1 positive cells in the bone marrow cell culture. Moreover, it effected the G-CSF mediated restoration of granulocytopoiesis in a murine leukopenia model.
Takizawa
M
M
Discovery Research Laboratories, Takeda Chemical Industries Ltd., Osaka, Japan.
Hida
T
T
Horiguchi
T
T
Hiramoto
A
A
Harada
S
S
Tanida
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005260:Female; D005285:Fermentation; D016179:Granulocyte Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism; D055666:Lipopeptides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D055666:Lipopeptides; D009842:Oligopeptides; C095335:TAN 1511 A; C095336:TAN 1511 B; C095337:TAN 1511 C; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor