Synthesis and biological evaluation of vioprolide B and its dehydrobutyrine-glycine analogue.

Herein, we describe the total synthesis of the depsipeptide vioprolide B and of an analogue, in which the ()-dehydrobutyrine amino acid was replaced by glycine. The compounds were studied in biological assays which revealed cytotoxicity solely for vioprolide B presumably by covalent binding to cysteine residues of elongation factor eEF1A1 and of chromatin assembly factor CHAF1A.

Target identification of usnic acid in bacterial and human cells.

Usnic acid is a natural product with versatile biological activities against various organisms. Here, we utilise a chemical proteomic strategy to gain insights into its target scope in bacterial and human cells. First, we excluded DNA binding as a major reason for its antibacterial activity, and second, we commenced with target profiling, which unravelled several metal cofactor-dependent enzymes in both species indicating a polypharmacological mode of action.

Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair.

Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment.

Pronucleotide Probes Reveal a Diverging Specificity for AMPylation vs UMPylation of Human and Bacterial Nucleotide Transferases.

AMPylation is a post-translational modification utilized by human and bacterial cells to modulate the activity and function of specific proteins. Major AMPylators such as human FICD and bacterial VopS have been studied extensively for their substrate and target scope . Recently, an AMP pronucleotide probe also facilitated the analysis of AMPylation in living cells.

Comparative Target Analysis of Chlorinated Biphenyl Antimicrobials Highlights MenG as a Molecular Target of Triclocarban.

Triclocarban (TCC), a formerly used disinfectant, kills bacteria via an unknown mechanism of action. A structural hallmark is its ,-diaryl urea motif, which is also present in other antibiotics, including the recently reported small molecule PK150. We show here that, like PK150, TCC exhibits an inhibitory effect on menaquinone metabolism via inhibition of the biosynthesis protein demethylmenaquinone methyltransferase (MenG).