Jeffrey N Johnston

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Chagas disease is a deadly infection caused by the protozoan parasite Trypanosoma cruzi. Afflicting approximately 8 million people in Latin America, Chagas disease is now becoming a serious global health problem proliferating beyond the traditional geographical borders, mainly because of human and vector migration. Because the disease is endemic in(More)
The effects of a selective beta 2-blocker (ICI 118,551) on hepatic haemodynamics were studied in cirrhotic and non-cirrhotic rats. Infusions of 10 and 20 microgram (kg body wt)-1 min-1 beta 2-blocker (in cirrhotic and non-cirrhotic rats) significantly reduced portal pressure, portal venous flow and liver blood flow without altering heart rate. Splanchnic(More)
The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein-protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers(More)
Therapeutics that induce cancer cell senescence can block cell proliferation and promote immune rejection. However, the risk of tumor relapse due to senescence escape may remain high due to the long lifespan of senescent cells that are not cleared. Here, we show how combining a senescence-inducing inhibitor of the mitotic kinase Aurora A (AURKA) with an(More)
Complex II superfamily members catalyze the kinetically difficult interconversion of succinate and fumarate. Due to the relative simplicity of complex II substrates and their similarity to other biologically abundant small molecules, substrate specificity presents a challenge in this system. In order to identify determinants for on-pathway catalysis,(More)
The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor(More)
Despite Nature's longstanding ability to use a proton, the most prevalent Lewis acid, to both activate and orient a substrate during an enantioselective reaction, this work represents the first example of this phenomenon outside of a protein. A chiral, nonracemic BisAMidine (BAM) ligand was designed, synthesized, and complexed to the proton of a Brønsted(More)
VNI is a potent inhibitor of CYP51 and was recently shown to achieve a parasitological cure of mice infected with T. cruzi in both acute and chronic stages of infection. T. cruzi is the causative parasite of Chagas disease, a neglected tropical disease. The first enantioselective chemical synthesis of VNI (at a materials cost of less than $0.10/mg) is(More)