dihydroeponemycin and epoxomicin

The interface of chemistry and biology offers many opportunities to explore different aspects of cell biology. The emerging field of chemical genetics is providing the chemical means to understand biological systems not easily accessible using classical genetic manipulations. In this article, we will discuss how natural product mode of action studies and novel bio-organic manipulation of intracellular protein levels are proving useful in the exploration of cell biology.

Topics: Animals; Biotinylation; Combinatorial Chemistry Techniques; Drug Design; Drug Evaluation, Preclinical; Genomics; Green Fluorescent Proteins; Humans; Ketones; Models, Chemical; Molecular Probe Techniques; Nanotechnology; Oligopeptides; Phosphorylation; Protein Binding; Proteins; Receptors, Androgen; Recombinant Fusion Proteins; Serine; Sesquiterpenes; Signal Transduction; Ubiquitin-Protein Ligases

While two structurally related epoxyketone-containing antitumor natural products, epoxomicin and eponemycin, share the proteasome as a common intracellular target, they differ in their antiproliferative activity, proteasome subunit binding specificity, and rates of proteasome inhibition. As a first step towards understanding such differences and developing novel proteasome subunit-specific inhibitors, we report here the synthesis and characterization of epoxomicin/dihydroeponemycin chimerae.

Topics: Cell Division; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Multienzyme Complexes; Oligopeptides; Proteasome Endopeptidase Complex; Serine; Substrate Specificity