New antitumor antibiotic, LL-D05139 beta. Fermentation, isolation, structure determination and biological activities.
The LL-D05139 complex, containing LL-D05139 beta and azaserine, was recovered from the fermentation filtrate of Glycomyces harbinensis (NRRL 15337). A chemically defined medium was developed which favored the production of LL-D05139 beta. Antibiotic LL-D05139 beta was isolated from the fermentation filtrate by adsorption on granular carbon and further purified by chromatography on microcrystalline cellulose. Acid hydrolysis of LL-D05139 beta gave one molar equivalent each of alanine and serine. Both amino acids were found to have the L-configuration by GC analysis on a chiral column and alanine was assigned to be the N-terminal amino acid by Edman degradation. This information coupled with IR, UV, 1H NMR, 13C NMR and MS spectral data allowed us to assign the structure of LL-D05139 beta as alanylazaserine. LL-D05139 beta demonstrated greater antibacterial and biochemical induction assay activities than azaserine. The two drugs showed similar antitumor activities.
American Cyanamid Co., Medical Research Division, Lederle Laboratories, Pearl River, New York 10965.
M D
MD
Lee
A A
AA
Fantini
N A
NA
Kuck
M
M
Greenstein
R T
RT
Testa
D B
DB
Borders
D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification / Q000494:pharmacology; D001377:Azaserine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification; D004249:DNA Damage; D005285:Fermentation; D005658:Fungi / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D012988:Soil Microbiology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000903:Antibiotics, Antineoplastic; D001377:Azaserine; C054841:LL D05139(beta)