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Papers by patrick gunning

Organic & Biomolecular Chemistry, 2005

The synthesis of a heteroditopic receptor which exhibits positive cooperativity for the binding o... more The synthesis of a heteroditopic receptor which exhibits positive cooperativity for the binding of phosphate ion pairs under physiological conditions. Optimised complementarity between crown ether host and metal guest leads to increased binding affinity, Ka.

MedChemComm, 2012

Evidence shows that signal transducer and activator of transcription 5 (Stat5) protein, a member ... more Evidence shows that signal transducer and activator of transcription 5 (Stat5) protein, a member of the STAT family of signalling proteins, plays a pivotal role in the progression of many human cancers including acute myeloid leukemias and prostate cancer. This mini-review outlines progress made towards identifying agents capable of silencing aberrant Stat5 signalling.

Hormone Molecular Biology and Clinical Investigation, 2000

Abstract Molecular approaches to inhibit STAT5 signaling have been hailed as a viable targeted an... more Abstract Molecular approaches to inhibit STAT5 signaling have been hailed as a viable targeted anticancer therapy. In particular, many drugs and drug candidates have been developed to successfully inhibit upstream effectors of STAT5 by indirectly targeting cell surface receptors and protein kinases (FLT-3, JAK2, and BCR-ABL). Indirect strategies have yielded potent agents, such as imatinib, AC2207, and EXEL823 which effectively silence STAT5 activity but which suffer from off-target effects and toxicity. This article will focus on reviewing the current literature pertaining to direct inhibitors of STAT5 protein and assess the prospects for a future STAT5-targeting therapeutic.

Carbohydrate Polymers, 2014

The growing social and economic consequences of pollution derived from plastics are focusing atte... more The growing social and economic consequences of pollution derived from plastics are focusing attention on the need to produce novel bioprocesses for enhancing food shelf-life. As a consequence, in recent years the use of edible films for food packaging is generating a huge scientific interest. In this work we report the production of an edible hydrocolloid film made by using Citrus pectin and the protein phaseolin crosslinked by microbial transglutaminase, an enzyme able to covalently modify proteins by formation of isopeptide bonds between glutamine and lysine residues. The films were characterized and their morphology was evaluated by both atomic force microscopy and scanning electron microscopy. Mechanical properties and barrier properties to CO 2 , O 2 and water vapor have demonstrated that these films possess technological features comparable to those possessed by commercial plastics. It is worth noting that these characteristics are maintained even following storage of the films at 4 • C or −20 • C, suggesting that our bioplastics can be tailored to protect food at low temperature. Moreover, gastric and duodenal digestion studies conducted under the same conditions found in the human digestion system have demonstrated that transglutaminase-containing films are regularly digested encouraging an application of the proposed materials as food coatings.

Chemical Science, Jan 2014

The insoluble glucan polymer starch is a major player in the human diet; it is also an important ... more The insoluble glucan polymer starch is a major player in the human diet; it is also an important bulk commodity. Nonetheless, our understanding of its biochemistry remains poor, not least because of the challenge of analysing enzymes that operate across the solid–liquid interface. In the present study, the enzymatic polymerisation of glucans immobilised on gold sensor chip and nanoparticle surfaces was achieved with Arabidopsis phosphorylase AtPHS2. The basis of the action of AtPHS2 on surface glucans could be rationalised through consideration of the X-ray crystal structure of this enzyme, which identified a previously unreported enzyme surface binding site for glucans. Extension of the glucan-coated sensor chip surfaces could be monitored in real time by SPR, enabling kinetic analysis of AtPHS2-mediated glucan synthesis, which showed similar efficiency to in solution analyses. Extension of both sensor and nanoparticles surfaces coated with glucan was analysed by TEM, which confirmed glucan polymerisation. The arrangement of newly formed glucan chains into ordered helical arrangements was evident from iodine staining, as well as from enzyme response characteristics that proved typical of starch-like material. As such, the glucan-modified sensor chip and nanoparticle surfaces represent novel tools with which to analyse starch-active enzymes.

Organic & Biomolecular Chemistry, 2005

The synthesis of a heteroditopic receptor which exhibits positive cooperativity for the binding o... more The synthesis of a heteroditopic receptor which exhibits positive cooperativity for the binding of phosphate ion pairs under physiological conditions. Optimised complementarity between crown ether host and metal guest leads to increased binding affinity, Ka.

MedChemComm, 2012

Evidence shows that signal transducer and activator of transcription 5 (Stat5) protein, a member ... more Evidence shows that signal transducer and activator of transcription 5 (Stat5) protein, a member of the STAT family of signalling proteins, plays a pivotal role in the progression of many human cancers including acute myeloid leukemias and prostate cancer. This mini-review outlines progress made towards identifying agents capable of silencing aberrant Stat5 signalling.

Hormone Molecular Biology and Clinical Investigation, 2000

Abstract Molecular approaches to inhibit STAT5 signaling have been hailed as a viable targeted an... more Abstract Molecular approaches to inhibit STAT5 signaling have been hailed as a viable targeted anticancer therapy. In particular, many drugs and drug candidates have been developed to successfully inhibit upstream effectors of STAT5 by indirectly targeting cell surface receptors and protein kinases (FLT-3, JAK2, and BCR-ABL). Indirect strategies have yielded potent agents, such as imatinib, AC2207, and EXEL823 which effectively silence STAT5 activity but which suffer from off-target effects and toxicity. This article will focus on reviewing the current literature pertaining to direct inhibitors of STAT5 protein and assess the prospects for a future STAT5-targeting therapeutic.

Carbohydrate Polymers, 2014

The growing social and economic consequences of pollution derived from plastics are focusing atte... more The growing social and economic consequences of pollution derived from plastics are focusing attention on the need to produce novel bioprocesses for enhancing food shelf-life. As a consequence, in recent years the use of edible films for food packaging is generating a huge scientific interest. In this work we report the production of an edible hydrocolloid film made by using Citrus pectin and the protein phaseolin crosslinked by microbial transglutaminase, an enzyme able to covalently modify proteins by formation of isopeptide bonds between glutamine and lysine residues. The films were characterized and their morphology was evaluated by both atomic force microscopy and scanning electron microscopy. Mechanical properties and barrier properties to CO 2 , O 2 and water vapor have demonstrated that these films possess technological features comparable to those possessed by commercial plastics. It is worth noting that these characteristics are maintained even following storage of the films at 4 • C or −20 • C, suggesting that our bioplastics can be tailored to protect food at low temperature. Moreover, gastric and duodenal digestion studies conducted under the same conditions found in the human digestion system have demonstrated that transglutaminase-containing films are regularly digested encouraging an application of the proposed materials as food coatings.

Chemical Science, Jan 2014

The insoluble glucan polymer starch is a major player in the human diet; it is also an important ... more The insoluble glucan polymer starch is a major player in the human diet; it is also an important bulk commodity. Nonetheless, our understanding of its biochemistry remains poor, not least because of the challenge of analysing enzymes that operate across the solid–liquid interface. In the present study, the enzymatic polymerisation of glucans immobilised on gold sensor chip and nanoparticle surfaces was achieved with Arabidopsis phosphorylase AtPHS2. The basis of the action of AtPHS2 on surface glucans could be rationalised through consideration of the X-ray crystal structure of this enzyme, which identified a previously unreported enzyme surface binding site for glucans. Extension of the glucan-coated sensor chip surfaces could be monitored in real time by SPR, enabling kinetic analysis of AtPHS2-mediated glucan synthesis, which showed similar efficiency to in solution analyses. Extension of both sensor and nanoparticles surfaces coated with glucan was analysed by TEM, which confirmed glucan polymerisation. The arrangement of newly formed glucan chains into ordered helical arrangements was evident from iodine staining, as well as from enzyme response characteristics that proved typical of starch-like material. As such, the glucan-modified sensor chip and nanoparticle surfaces represent novel tools with which to analyse starch-active enzymes.