Gunning, Patrick

Ph.D. | Associate ProfessorChemistry - Organic & Inorganic Synthesis
Picture of Patrick Gunning

Contact Information

Phone: 
905 828.5354
Fax: 
905 828.5425
Room: 
DV4046
Mailing Address: 
3359 Mississauga Road North
City: 
Mississauga
Province: 
Ontario
Postal Code: 
L5L 1C6

Research

Patrick picture of research Most biological processes involve permanent and nonpermanent interactions between different proteins. Many protein complexation events play key roles in various human diseases. The thrust of our research focuses on the development of novel, small molecule architectures to reverse a protein's aberrant role, via manipulation of protein complexation events. Numerous protein-protein interfaces contain compact, centralized regions of residues, known as 'hot spots', crucial for interaction. Many proteins function by binding to multiple partners and these proteins tend to use the same hot spots, which can adapt to present the same residues in different structural contexts.

Our research seeks to design and develop scaffolds to artificially suppress or up-regulate specific gene expression profiles via manipulation of protein-protein interactions, thereby inducing therapeutically-beneficial cellular responses in malfunctioning human cells. The proposed research seeks to validate whether protein function can be 'switched' on or off through artificial protein complexation by divalent conjugated small molecule 'hot spot' recognition agents. Molecular modulation of specific protein-protein interactions offers a dynamic approach to artificially regulating aberrant protein activity in human disease. A keen objective of the proposed work is to promote and illuminate the efficacy of developing novel drug-like scaffolds incorporating inorganic, as well as organic, functionality to achieve in vivo manipulation of cellular signaling.

Publications

Siddiquee, K. A. Z., Gunning, P. T., Glenn, M., Katt, W. P., Zhang, S., Schroeck, C., Sebti, S. M., Jove, R., Hamilton, A. D., Turkson, J. "Selective disruption of Stat3 dimerization by an oxazole based novel small molecule alters intracellular Stat3 processing and inhibits tumor cell survival, migration and invasion, and growth of human breast tumor xenografts." ACS Chemical Biology 2007, in press.

Gunning, P. T., Glenn, P., Turkson, J., Kim, J. S., Katt, W. P., Sebti, S. M., Jove, R., Hamilton, A. D. "Isoform Selective Inhibition of Stat1 or Stat3 Homodimerization via Peptidomimetic Probes: Structural Recognition of Stat SH2 Domains." Bio. Org. Med. Chem. Lett. 2006, 7, 1875-1878.

Fielden, J., Gunning, P. T., Long, D-L., Ellern, A., Nutley, M., K̀‚gerler, P., Cronin, L. "Anion Control of Isomerism, Crystal Packing and Phosphate Binding in a Mononuclear Zinc Complex." Polyhedron 2006, 25, 3474.

Gunning, P. T. "Positive Ion-Pair Cooperativity Exhibited for the Binding of Phosphate Under Physiological Conditions." Org. Biomol. Chem. 2005, 3, 3877.

Gunning, P. T., Benniston, A. C., Peacock, R. D. " Synthesis and Binding Properties of Hybrid Cyclophane-Azamacrocyclic Receptors." J. Org. Chem. 2005, 70, 115.

Gunning, P. T., Peacock, R. D., Benniston, A. C. "Modular Ditopic Crown-Shielded Phosphate Ion Pair Receptor." Chem.Commun. 2004, 2226.

Siddiquee, K. A. Z., Gunning, P. T., Glenn, M., Katt, W. P., Zhang, S., Schroeck, C., Sebti, S. M., Jove, R., Hamilton, A. D., Turkson, J. "Selective disruption of Stat3 dimerization by an oxazole based novel small molecule alters intracellular Stat3 processing and inhibits tumor cell survival, migration and invasion, and growth of human breast tumor xenografts." ACS Chemical Biology 2007, in press.

Gunning, P. T., Glenn, P., Turkson, J., Kim, J. S., Katt, W. P., Sebti, S. M., Jove, R., Hamilton, A. D. "Isoform Selective Inhibition of Stat1 or Stat3 Homodimerization via Peptidomimetic Probes: Structural Recognition of Stat SH2 Domains." Bio. Org. Med. Chem. Lett. 2006, 7, 1875-1878.

Fielden, J., Gunning, P. T., Long, D-L., Ellern, A., Nutley, M., K̀‚gerler, P., Cronin, L. "Anion Control of Isomerism, Crystal Packing and Phosphate Binding in a Mononuclear Zinc Complex." Polyhedron 2006, 25, 3474.

Gunning, P. T. "Positive Ion-Pair Cooperativity Exhibited for the Binding of Phosphate Under Physiological Conditions." Org. Biomol. Chem. 2005, 3, 3877.

Gunning, P. T., Benniston, A. C., Peacock, R. D. " Synthesis and Binding Properties of Hybrid Cyclophane-Azamacrocyclic Receptors." J. Org. Chem. 2005, 70, 115.

Gunning, P. T., Peacock, R. D., Benniston, A. C. "Modular Ditopic Crown-Shielded Phosphate Ion Pair Receptor." Chem.Commun. 2004, 2226.