Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger

Abstract

In the course of our screening program for regulators of the expression of GRP78 molecular chaperone, JBIR-04 (1) and -05 (2) were isolated from Streptomyces violaceoniger 4541-SVS3 as congeners of prunustatin A (3). The structures of 1 and 2 were determined by the analyses of the spectroscopic data. These compounds mainly consist of an amino acid and amino acid derived a -hydroxy acid residues. 1 and 2 inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells, but their activities were highly reduced compared with those of 3 and SW-163A.

Antimycin-type depsipeptides: discovery, biosynthesis, chemical synthesis, and bioactivities

“…41 Decades later, two other neoantimycins differing at R 1 and R 2 , SW-163A (54) and B (55), were isolated from Streptomyces sp. 45 Similarly, neoantimycins D (60) and E (61), which were recently isolated from S. orinoci along with 53-56 and 59 possess a 3-aminosalicyclic acid, 43 while unantimycin A (62) produced by Streptomyces sp. 42 More recently, neoantimycins F (56) and G (57) were isolated from S. orinoci, and their structures and absolute congurations were also determined by NMR and chemical degradation and derivatization analyses.…”

Rare Streptomyces N-Formyl Amino-salicylamides Inhibit Oncogenic K-Ras

“…Planar structures for SW-163A ( 9 ) and SW-163B ( 10 ) were reported in 2001 9 from a Japanese soil Streptomyces sp. (SNA15986), while the planar structures for prunustatin A ( 11 ), and JBIR-04 ( 12 ) and JBIR-05 ( 13 ), were reported in 2005 10 and 2007 11 respectively from the Okinawan soil Streptomyces violaceoniger (4521-SVS3), as down-regulators of the molecular chaperone GRP-78. The absolute configurations of 9 and 11 were subsequently determined in 2007 12 by chemical degradation and derivatization.…”

JBIR-52, a new antimycin-like compound, from Streptomyces sp. ML55

“…Hence, the activities of GRP78 suppression by these compounds were considered to depend on respiratory inhibition due to salicylic JBIR-52, a new antimycin-like compound I Kozone et al acid moiety. 14 These results provide us the interesting information that the size of macrocyclic structure determines the inhibitory activity of GRP78 expression by salicylic acid function. Studies in the detailed biological activities are now underway.…”

“…Thus, a 2,6-dimethyl-3-oxo-4-oxyheptanoic acid moiety was elucidated as a partial structure of 1 (Figure 1b Figure 1b) and the UV spectrum of 1 also suggested the existence of the 3-(formylamino)-2-hydroxybenzoyl moiety, which is the same chromophore as those of the antimycin-related compounds. [12][13][14][15] The sequence from an amide proton 6-NH (d H 7.10) to a methyl proton 26-H (d H 1.38) through an a-methine proton 6-H (d H 5.29) and an oxymethine proton 7-H (d H 5.60) was observed in the DQF-COSY spectrum of 1. In addition to these correlations, the long-range couplings from the methine proton 6-H to a carbonyl carbon C-5 (d C 168.8) and the amide carbonyl carbon C-18 were observed.…”