title: Generation of novel rapamycin structures by microbial manipulations.
abstract: 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.
authors.affiliation: Central Research Division, Pfizer Pharmaceuticals Inc., Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishida
authors.forename: T
authors.initials: T
authors.lastname: Sakakibara
authors.forename: F
authors.initials: F
authors.lastname: Aoki
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Inagaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: L H
authors.initials: LH
authors.lastname: Huang
authors.forename: M A
authors.initials: MA
authors.lastname: Guadliana
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus