Jeffrey N Johnston

Learn 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)
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)
BACKGROUND In Jamaica the reported incidence of AIDS increased from 0.1/100000 in 1985 to 20.2/100000 in 1995. Here there is great reluctance to have voluntary blood testing and, indeed, any blood testing. Since only enzyme-linked immunoassay (EIA) was available for screening serum HIV-1 and 2 antibody, it was considered that a non-invasive saliva screening(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)
A new means to activate diazoalkanes has been discovered and applied broadly over the past few years. Brønsted acids, both achiral and chiral, have been used to promote the formation of carbon-carbon and carbon-heteroatom bonds with a growing number of diazoalkane derivatives. Aside from their straightforward ability to build structural and stereochemical(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)
The amide bond is one of nature's most common functional and structural elements, as the backbones of all natural peptides and proteins are composed of amide bonds. Amides are also present in many therapeutic small molecules. The construction of amide bonds using available methods relies principally on dehydrative approaches, although oxidative and(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)
The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the(More)