Generation of novel rapamycin structures by microbial manipulations.
A new rapamycin producing culture was isolated and designated as Actinoplanes sp. N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding using this culture, and biotransformation approaches generated new rapamycin analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or C-39. The immunosuppressive activity of the resulting analogs was established in the mixed lymphocyte reaction assay.
Nishida
H
H
Central Research Division, Pfizer Pharmaceuticals Inc., Aichi, Japan.
Sakakibara
T
T
Aoki
F
F
Saito
T
T
Ichikawa
K
K
Inagaki
T
T
Kojima
Y
Y
Yamauchi
Y
Y
Huang
L H
LH
Guadliana
M A
MA
D000192:Actinomycetales / Q000145:classification / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001711:Biotransformation; D065607:Cytochrome P-450 Enzyme Inhibitors; D005285:Fermentation; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D008214:Lymphocytes / Q000187:drug effects; D015394:Molecular Structure; D011090:Polyenes / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D020123:Sirolimus
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus