High OGT activity is essential for MYC-driven proliferation of prostate cancer cells.

O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. OGT modifies intra-cellular proteins via single sugar conjugation (O-GlcNAcylation) to alter their activity. We recently discovered the first fast-acting OGT inhibitor OSMI-2.

Small Molecule Potentiation of Gram-Positive Selective Antibiotics against .

In 2016, the World Health Organization deemed antibiotic resistance one of the biggest threats to global health, food security, and development. The need for new methods to combat infections caused by antibiotic resistant pathogens will require a variety of approaches to identifying effective new therapeutic strategies. One approach is the identification of small molecule adjuvants that potentiate the activity of antibiotics of demonstrated utility, whose efficacy is abated by resistance, both acquired and intrinsic.

Analogue synthesis reveals decoupling of antibiofilm and β-lactam potentiation activities of a lead 2-aminoimidazole adjuvant against Mycobacterium smegmatis.

Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro, it expresses phenotypic resistance to antimicrobial drugs. As the in vivo survival of M.

Small molecule adjuvants that suppress both chromosomal and mcr-1 encoded colistin-resistance and amplify colistin efficacy in polymyxin-susceptible bacteria.

Bacterial resistance to polymyxin antibiotics has taken on a new and more menacing form. Common are genomically-encoded resistance mechanisms to polymyxins, specifically colistin (polymyxin E), however, the plasmid-borne mobile colistin resistance-1 (mcr-1) gene has recently been identified and poses a new threat to global public health. Within six months of initial identification in Chinese swine in November 2015, the first human clinical isolation in the US was reported (Apr.

Hospital to Home: A Quality Improvement Initiative to Implement High-fidelity Simulation Training for Caregivers of Children Requiring Long-term Mechanical Ventilation.

Background: Preparing families of children requiring long-term mechanical ventilation (LTMV) to manage medical emergencies at home is challenging. Opportunities for family caregivers to rehearse crisis management in a controlled setting before discharge are limited.

Objective: We aimed to create a multimodal discharge preparedness curriculum, incorporating high-fidelity simulation training, to prepare family caregivers of children with complex medical conditions requiring long-term mechanical ventilation.

Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism.

Metabolic networks are highly connected and complex, but a single enzyme, O-GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179).

A synthetic lethal approach for compound and target identification in Staphylococcus aureus.

The majority of bacterial proteins are dispensable for growth in the laboratory but nevertheless have important physiological roles. There are no systematic approaches to identify cell-permeable small-molecule inhibitors of these proteins. We demonstrate a strategy to identify such inhibitors that exploits synthetic lethal relationships both for small-molecule discovery and for target identification.

A three-step process to facilitate the annulation of polycyclic aromatic hydrocarbons.

A new efficient three-step process to annulate polycyclic aromatic hydrocarbons (PAHs) has been developed, providing access to PAHs with saturated rings that under current chemical methods would be difficult to produce in an efficient manner. This method relies on a palladium-catalyzed cross-coupling reaction of various brominated PAHs with cyclohexanone to yield α-arylated ketones, which are converted to regiospecific vinyl triflates and cyclized by a palladium-catalyzed intramolecular arene-vinyl triflate coupling to produce PAHs with incorporated saturated rings or "tetrahydroindeno-annulated" PAHs.

The First Example of Nickel-Catalyzed Silyl-Heck Reactions: Direct Activation of Silyl Triflates Without Iodide Additives.

For the first time, nickel-catalyzed silyl-Heck reactions are reported. Using simple phosphine-supported nickel catalysts, direct activation of silyl triflates has been achieved. These results contrast earlier palladium-catalyzed systems, which require iodide additives to activate silyl-triflates.

Preparation of vinyl silyl ethers and disiloxanes via the silyl-Heck reaction of silyl ditriflates.

Vinyl silyl ethers and disiloxanes can now be prepared from aryl-substituted alkenes and related substrates using a silyl-Heck reaction. The reaction employs a commercially available catalyst system and mild conditions. This work represents a highly practical means of accessing diverse classes of vinyl silyl ether substrates in an efficient and direct manner with complete regiomeric and geometric selectivity.

Preparation of allyl and vinyl silanes by the palladium-catalyzed silylation of terminal olefins: a silyl-Heck reaction.

A high-yielding protocol for the palladium-catalyzed silylation of terminal alkenes using silyl halides is reported. This method allows facile conversion of styrenes to -β-silyl styrenes using either TMSI or TMSCl/LiI. Terminal allyl silanes with good ratios are also readily accessed from α-olefins by this method.