New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6.
Four novel glycosylated derivatives of versipelostatin (1), versipelostatins B-E (2-5), were isolated from the culture broth of Streptomyces versipellis 4083-SVS6. The inhibitory activities of the isolated compounds against the expression of molecular chaperone GRP78 induced by 2-deoxyglucose were evaluated. Of the five versipelostatin family members, 1 and 4 were the more potent with IC(50) values of 3.5 and 4.3 microM. These results suggest that the alpha-L-oleandropyranosyl (1-->4)-beta-D-digitoxopyranosyl residue in the sugar moiety may play an important role in down-regulating GRP78 expression induced by 2-deoxyglucose.
Zhao
Ping
P
Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-8657, Japan.
Ueda
Jun-ya
JY
Kozone
Ikuko
I
Chijiwa
Shuhei
S
Takagi
Motoki
M
Kudo
Fumitaka
F
Nishiyama
Makoto
M
Shin-ya
Kazuo
K
Kuzuyama
Tomohisa
T
D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006031:Glycosylation; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D018942:Macrolides / Q000302:isolation & purification / Q000494:pharmacology*; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008968:Molecular Conformation; D009844:Oligosaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018942:Macrolides; D018832:Molecular Chaperones; D009844:Oligosaccharides; C490154:versipelostatin