Complete stereochemistry and preliminary structure-activity relationship of rakicidin A, a hypoxia-selective cytotoxin from Micromonospora sp.
The complete stereochemistry of rakicidin A, a hypoxia-selective cytotoxin produced by Micromonospora sp., was unambiguously established by extensive chemical degradation and derivatization studies. During the PGME derivatization-based configurational analysis of 3-hydroxy-2,4,16-trimethylheptadecanoic acid, an irregular Δδ distribution was observed, which necessitated further acylation of the 3-hydroxy group to resolve the inconsistency. A hydrogenated derivative of rakicidin A, its ring-opened product, and two congeners with different alkyl chain lengths were tested for hypoxia-selective cytotoxicity. The results indicated that both the conjugated diene unit and appropriate chain length are essential for the unique activity of rakicidin A.
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University , 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Naoya
N
Oku
Shouhei
S
Matoba
Yohko Momose
YM
Yamazaki
Ryoko
R
Shimasaki
Satoshi
S
Miyanaga
Yasuhiro
Y
Igarashi
D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D055666:Lipopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D047630:Depsipeptides
D003603:Cytotoxins; D055666:Lipopeptides; D010456:Peptides, Cyclic; C000723972:rakicidins; D047630:Depsipeptides