title: New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6.
abstract: 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.
authors.affiliation: Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-8657, Japan.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Jun-ya
authors.initials: JY
authors.lastname: Ueda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kozone
authors.forename: Shuhei
authors.initials: S
authors.lastname: Chijiwa
authors.forename: Motoki
authors.initials: M
authors.lastname: Takagi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kudo
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
mesh_terms: 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*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018942:Macrolides; D018832:Molecular Chaperones; D009844:Oligosaccharides; C490154:versipelostatin