TMC-89A and B, new proteasome inhibitors from streptomyces sp. TC 1087.
نویسندگان
چکیده
ubiquitin, and then degraded by a proteasome in an ATP dependent manner1^ The catalytic core of the proteasome is the 20S proteasome. New20S proteasome inhibitors would contribute to further understanding of the system2~4\ In the course of our screening program, wehave isolated several classes of 20S proteasome inhibitors including (i) the novel cyclic peptides, TMC-95s, and (ii) the new members of a',/3'-epoxyketone containing peptides, TMC-86s and
منابع مشابه
Taxonomy, Production, Isolation, and Biological Activities
In our course of screening for novel proteasome inhibitors, TMC-95A and its diastereomers, TMC-95Bto D, were isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093. TMC-95Ainhibited the chymotrypsin-like (ChT-L), trypsin-like (TL), and peptidylglutamyl-peptide hydrolyzing (PGPH) activities of 20S proteasome with IC50 values of 5.4nM, 200nM, and 60nM, respectively. TMC-95Binhi...
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A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analo...
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ورودعنوان ژورنال:
- The Journal of antibiotics
دوره 53 9 شماره
صفحات -
تاریخ انتشار 2000