49824-43-3Relevant articles and documents
Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I
Amatuni, Alexander,Shuster, Anton,Adibekian, Alexander,Renata, Hans
, p. 1318 - 18,1326 (2020/09/02)
Amatuni et al. established a concise chemoenzymatic synthesis of cepafungin I. The route enabled access to a chemoproteomic probe, revealing high selectivity for proteasome subunits β5/2. Potent inhibition was associated with the macrocyclic hydroxyl group and lipid tail. Cepafungin I exhibited similar mode of action with the clinical drug bortezomib. The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I toward the β2 and β5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I.
Characterization of FabG and FabI of the Streptomyces coelicolor dissociated fatty acid synthase
Singh, Renu,Reynolds, Kevin A.
, p. 631 - 640 (2015/03/31)
Streptomyces coelicolor produces fatty acids for both primary metabolism and for biosynthesis of the secondary metabolite undecylprodiginine. The first and last reductive steps during the chain elongation cycle of fatty acid biosynthesis are catalyzed by FabG and FabI. The S. coelicolor genome sequence has one fabI gene (SCO1814) and three likely fabG genes (SCO1815, SCO1345, and SCO1846). We report the expression, purification, and characterization of the corresponding gene products. Kinetic analyses revealed that all three FabGs and FabI are capable of utilizing both straight and branched-chain β-ketoacyl-NAC and enoyl-NAC substrates, respectively. Furthermore, only SCO1345 differentiates between ACPs from both biosynthetic pathways. The data presented provide the first experimental evidence that SCO1815, SCO1346, and SCO1814 have the catalytic capability to process intermediates in both fatty acid and undecylprodiginine biosynthesis.
Group of anti-cancer compounds with specific structure and their production method
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Page/Page column 26, (2010/11/23)
Compounds containing a specific branched chain end terminal group, which is isopropyl, sec.-butyl, or tert.-butyl; a polar leading group; and long-chain aliphatic, non-cyclic, saturated or unsaturated, hydrocarbon group linking them; and having anti-cancer and immune boosting activity.