Chemical compounds produced by organisms, or natural products, are excellent sources of inspiration for anticancer pharmaceutical discovery (Rodrigues et al., 2016). Microtubule targeting agents are a specific class of compounds, often discovered from natural sources, that have been developed as clinically successful anticancer therapies (Steinmetz and Prota, 2018). In the...
A more quantitative understanding of peptide entrapment and elution from otherwise protein-repellent polyethylene oxide (PEO) brush layers will provide direction for development of new strategies for drug storage and delivery. Here we describe criteria for peptide integration and structural change within the PEO brush, and discuss the reversibility of peptide...
Ribomimetic natural products have long been known for their important biological activities. Structurally, they contain a densely functionalized cyclopentane unit that resembles ribose. Pactamycin, the prominent member of this class of natural products, is a potent protein synthesis inhibitor produced by the soil bacterium Streptomyces pactum. In pactamycin, the aminocyclopentitol...
Superwarfarins are anticoagulant rodenticides that are 100 times more potent and 15 times more persistent than warfarin. They have been used since the 1980s and cause over 10,000 cases of accidental and intentional poisonings per year. Apart from inducing uncontrollable bleeding, by inhibiting the vitamin K cycle, superwarfarins can disrupt...
An increased understanding of secondary metabolism in fungi is important for both biological and societal reasons. The ascomycete genus, Tolypocladium, is an ideal system to explore secondary metabolism characterization, ecology, evolution and regulation. The genus produces and has the genomic potential to produce a wide array of metabolites. Paired with...
Pharmaceuticals, molecular catalysts, and secondary metabolites often contain nitrogen. The problems faced synthesizing compounds which contain nitrogen was because of the Lewis base reactivity of nitrogen lone pairs, and the acidic protons of some nitrogenous functional groups. We developed two methods for the synthesis of nitrogeous compounds. Additionally, we successfully...
The sexually transmitted disease gonorrhea, caused by the Gram-negative bacterium and obligate human pathogen Neisseria gonorrhoeae, remains a significant health and economic burden worldwide. In the absence of a protective vaccine, antimicrobial agents are the only pharmacological intervention for patients with gonorrhea. However, due to the remarkable ability of gonococcus...
Natural products from both terrestrial and marine sources represent a significant source of novel drug leads, and have previously been developed into clinically-approved agents for the treatment of various human diseases. This work represents the biological characterization of the mechanistic basis for activity of several natural product structures in models...
The continued propagation of antibiotic resistance requires the development of new therapeutics. The lipopeptide antibiotic enduracidin has demonstrated high activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus. In addition to a lack of cross-resistance with existing antibiotic classes, enduracidin has no known transferrable resistance mechanism. The development of enduracidin as...
Coibamide A is a methyl-stabilized cyclic depsipeptide with a lariat side chain that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups program based in Panama. Previous testing of this potent and selective growth-inhibitory agent in the National Cancer Institute (NCI) in vitro 60 human...