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Abstract
The aromatic polyketide tetracenomycin X (TcmX) was recently found to be a potent inhibitor of protein synthesis, whose binding site is located in a unique locus within the tunnel of the large ribosomal subunit. The distinct mode of action makes this relatively narrow class of macrolides promising for drug development, in our quest to prevent the spread of drug resistant pathogens. Here we report the isolation and structure elucidation of novel natural tetracenomycin X congener – 6-hydroxytetraceonomycin X (6-OH-TcmX). In contrast to TcmX, 6-OH-TcmX exhibited lower antimicrobial and cytotoxic activity, but comparable in vitro protein synthesis inhibition ability. A survey on spectral properties of tetracenomycins showed profound differences in both UV-absorption and fluorescence spectra of TcmX and 6-OH-TcmX, suggesting the significant influence of 6-hydroxylation on tetracenomycin chromophore. Nonetheless, characteristic spectral properties of tetracenomycins make them suitable candidates as a foundation for semi-synthetic drug development (e.g., for targeted delivery, theranostics or cell imaging).
Supplementary materials
Title
Biological evaluation and spectral characterization of novel tetracenomycin X congener
Description
Figure S1. HPLC traces of pure samples of TcmX and 6-OH-TcmX
Figure S2. 1H spectrum of 6-OH-TcmX recorded in CDCl3 at 600 MHz and 298K.
Figure S3. 2D ROESY spectrum (320 ms mixing time) of 6-OH-TcmX16 recorded in CDCl3 at 600 MHz and 298K.
Figure S4. Overlay of 2D 13C-1H HSQC (blue) and 13C-1H HMBC (red) NMR spectra of 6-OH-TcmX recorded in CDCl3 at 600 MHz and 298K.
Figure S5. 13C spectrum of 6-OH-TcmX recorded in CDCl3 at 600 MHz and 298K.
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