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Thomas R Jackson, Jeremy S Springall,
Damien Rogalle,
Naoko Masumoto,
Hung Ching Li,
François D'Hooge,
Semali P Perera,
Toby A Jenkins,
Tony D James,
John S Fossey,
Jean M H van den Elsen
Electrophoresis 02/2009; 29(24):5067. · 3.30 Impact Factor
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Nigel Vicker,
Christopher M. Sharland,
Wesley B. Heaton,
Ana M. Ramos Gonzalez,
Helen V. Bailey,
Andrew Smith, Jeremy S. Springall,
Joanna M. Day,
Helena J. Tutill,
Michael J. Reed,
Atul Purohit,
Barry V. L. Potter
Molecular and Cellular Endocrinology 01/2009; 301(1-2):259-265. · 4.19 Impact Factor
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Thomas R Jackson, Jeremy S Springall,
Damien Rogalle,
Naoko Masumoto,
Hung Ching Li,
François D'Hooge,
Semali P Perera,
A Toby A Jenkins,
Tony D James,
John S Fossey,
Jean M H van den Elsen
[show abstract]
[hide abstract]
ABSTRACT: The incorporation of specialised carbohydrate affinity ligand methacrylamido phenylboronic acid in polyacrylamide gels for fluorophore-assisted carbohydrate electrophoresis greatly improved the effective separation of saccharides that show similar mobilities in standard electrophoresis. Polyacrylamide gel electrophoresis using methacrylamido phenylboronic acid in low loading (typically 0.5-1% dry weight) was unequivocally shown to alter retention of labelled saccharides depending on their boronate affinity. While conventional fluorophore-assisted carbohydrate electrophoresis of 2-aminoacridone labelled glucose oligomers showed an inverted parabolic migration, an undesired trait of small oligosaccharides labelled with this neutral fluorophore, boron affinity saccharide electrophoresis separation of these carbohydrates completely restored their predicted running order, based on their charge/mass ratio, and resulted in improved separation of the analyte saccharides. These results exemplify boron affinity saccharide electrophoresis as an important new technique for analysing carbohydrates and sugar-containing molecules.
Electrophoresis 11/2008; 29(20):4185-91. · 3.30 Impact Factor
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Nigel Vicker,
Christopher M Sharland,
Wesley B Heaton,
Ana M Ramos Gonzalez,
Helen V Bailey,
Andrew Smith, Jeremy S Springall,
Joanna M Day,
Helena J Tutill,
Michael J Reed,
Atul Purohit,
Barry V L Potter
[show abstract]
[hide abstract]
ABSTRACT: 17beta-Hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is expressed at high levels in the testes and seminal vesicles but has also been shown to be present in prostate tissue, suggesting its potential involvement in both gonadal and non-gonadal testosterone biosynthesis. The role of 17beta-HSD3 in testosterone biosynthesis makes this enzyme an attractive molecular target for small molecule inhibitors for the treatment of prostate cancer. Here we report the design of selective inhibitors of 17beta-HSD3 as potential anti-cancer agents. Due to 17beta-HSD3 being a membrane-bound protein a crystal structure is not yet available. A homology model of 17beta-HSD3 has been built to aid structure-based drug design. This model has been used with docking studies to identify a series of lead compounds that may give an insight as to how inhibitors interact with the active site. Compound 1 was identified as a potent selective inhibitor of 17beta-HSD3 with an IC(50)=700nM resulting in the discovery of a novel lead series for further optimisation. Using our homology model as a tool for inhibitor design compound 5 was discovered as a novel potent and selective inhibitor of 17beta-HSD3 with an IC(50) approximately 200nM.
Molecular and Cellular Endocrinology 09/2008; 301(1-2):259-65. · 4.19 Impact Factor
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Nigel Vicker,
Christopher M. Sharland,
Wesley B. Heaton,
Ana M. Ramos Gonzalez,
Helen V. Bailey,
Andrew Smith, Jeremy S. Springall,
Joanna M. Day,
Helena J. Tutill,
Michael J. Reed,
Atul Purohit,
Barry V.L. Potter
[show abstract]
[hide abstract]
ABSTRACT: 17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed at high levels in the testes and seminal vesicles but has also been shown to be present in prostate tissue, suggesting its potential involvement in both gonadal and non-gonadal testosterone biosynthesis. The role of 17β-HSD3 in testosterone biosynthesis makes this enzyme an attractive molecular target for small molecule inhibitors for the treatment of prostate cancer.Here we report the design of selective inhibitors of 17β-HSD3 as potential anti-cancer agents. Due to 17β-HSD3 being a membrane-bound protein a crystal structure is not yet available. A homology model of 17β-HSD3 has been built to aid structure-based drug design. This model has been used with docking studies to identify a series of lead compounds that may give an insight as to how inhibitors interact with the active site. Compound 1 was identified as a potent selective inhibitor of 17β-HSD3 with an IC50 = 700 nM resulting in the discovery of a novel lead series for further optimisation. Using our homology model as a tool for inhibitor design compound 5 was discovered as a novel potent and selective inhibitor of 17β-HSD3 with an IC50 ∼200 nM.
Molecular and Cellular Endocrinology.
