Synthesis and biological activities of TAN-1511 analogues.
TAN-1511 analogues were synthesized and their effects on the proliferation of bone marrow cells were examined. To exert potent activity the following conditions are necessary: the configuration of the 2-amino-6,7-dihydroxy-4-thiaheptanoic acid moiety must be (2R,6R), long chain acyl groups (C14 to C18) must be bound to both hydroxyl groups, the amino group must be free or acylated with the long chain fatty acid (ca. C14) and the peptide moiety must have glutamic acid as a component. Among the synthesized compounds, trisodium (2R,6R)-2-amino-6,7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate, which has improved solubility, was effective in experimental leukocytopenia in mice.
Hida
T
T
Discovery Research Laboratory, Takeda Chemical Industries, Ltd., Osaka, Japan.
Hayashi
K
K
Yukishige
K
K
Tanida
S
S
Kawamura
N
N
Harada
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000627:therapeutic use; D005260:Female; D007970:Leukopenia / Q000188:drug therapy; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000627:therapeutic use; D010455:Peptides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D009842:Oligopeptides; D010455:Peptides