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.
Lee
M D
MD
American Cyanamid Co., Medical Research Division, Lederle Laboratories, Pearl River, New York 10965.
Fantini
A A
AA
Kuck
N A
NA
Greenstein
M
M
Testa
R T
RT
Borders
D B
DB
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)