Search

Your search keyword '"Paul W. Bowyer"' showing total 3 results
Start Over Author "Paul W. Bowyer" Publisher portland press ltd.
3 results on '"Paul W. Bowyer"'

1. Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum

Author

Deborah F. Smith, Ruwani S. Gunaratne, Paul W. Bowyer, Sasala R. Wickramsinghe, Chrislaine Withers-Martinez, Edward W. Tate, Katherine A. Brown, Robin J. Leatherbarrow, Anthony A. Holder, and Munira Grainger

Subjects
Plasmodium falciparum, Protozoan Proteins, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, law.invention, Antimalarials, 03 medical and health sciences, chemistry.chemical_compound, law, medicine, Animals, Benzothiazoles, Enzyme Inhibitors, Molecular Biology, Escherichia coli, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Cell Biology, N-Myristoylation, biology.organism_classification, Recombinant Proteins, 0104 chemical sciences, 3. Good health, Enzyme, Scintillation proximity assay, chemistry, Benzothiazole, Codon usage bias, Recombinant DNA, Acyltransferases, Research Article
Abstract

Recombinant N-myristoyltransferase of Plasmodium falciparum (termed PfNMT) has been used in the development of a SPA (scintillation proximity assay) suitable for automation and high-throughput screening of inhibitors against this enzyme. The ability to use the SPA has been facilitated by development of an expression and purification system which yields considerably improved quantities of soluble active recombinant PfNMT compared with previous studies. Specifically, yields of pure protein have been increased from 12 μg·l−1 to >400 μg·l−1 by use of a synthetic gene with codon usage optimized for expression in an Escherichia coli host. Preliminary small-scale ‘piggyback’ inhibitor studies using the SPA have identified a family of related molecules containing a core benzothiazole scaffold with IC50 values 80% at a concentration of 10 μM.

Published
2007

2. Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major

Author

Robin J. Leatherbarrow, Helen P. Price, Paul W. Bowyer, Katherine A. Brown, Chrysoula Panethymitaki, and Deborah F. Smith

Subjects
Antifungal Agents, Time Factors, Trypanosoma brucei brucei, Saccharomyces cerevisiae, Trypanosoma brucei, Biochemistry, Microbiology, parasitic diseases, Escherichia coli, Animals, Leishmania major, Enzyme Inhibitors, Candida albicans, Molecular Biology, chemistry.chemical_classification, Cryptococcus neoformans, biology, Cell Biology, biology.organism_classification, Leishmania, Recombinant Proteins, Kinetics, Enzyme, chemistry, Protozoa, Acyltransferases, Research Article
Abstract

The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC50 values of

Published
2006

3. Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum.

Author

Paul W. Bowyer, Ruwani S. Gunaratne, Munira Grainger, Chrislaine Withers-martinez, Sasala R. Wickramsinghe, Edward W. Tate, Robin J. Leatherbarrow, Katherine A. Brown, Anthony A. Holder, and Deborah F. Smith

Subjects
*PLASMODIUM falciparum, *ENZYMES, *ESCHERICHIA coli, *PROTEINS, *ENTEROBACTERIACEAE
Abstract

Recombinant N-myristoyltransferase of Plasmodium falciparum (termed PfNMT) has been used in the development of a SPA (scintillation proximity assay) suitable for automation and high-throughput screening of inhibitors against this enzyme. The ability to use the SPA has been facilitated by development of an expression and purification system which yields considerably improved quantities of soluble active recombinant PfNMT compared with previous studies. Specifically, yields of pure protein have been increased from 12 μg·l−1 to >400 μg·l−1 by use of a synthetic gene with codon usage optimized for expression in an Escherichia coli host. Preliminary small-scale ‘piggyback’ inhibitor studies using the SPA have identified a family of related molecules containing a core benzothiazole scaffold with IC50 values 80% at a concentration of 10 μM. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results