Biosciences Graduate Program

Daniel M. Quinn, BS, PhD

Portrait

Professor of Chemistry

Contact Information

Office: 315 CB
Iowa City, IA 52242
Office Phone: 319-335-335

Email: daniel-quinn@uiowa.edu
Web: More About Dr. Quinn - Related Websites and Resources

Education

BS, Chemistry, Quincy University
PhD, Bioorganic Chemistry, University of Kansas

Post Doctoral, Biological Chemistry, Indiana University
Post Doctoral, Biological Chemistry, University of Cincinnati

Education/Training Program Affiliations

Biosciences Graduate Program

Research Summary

The cholinesterase family of enzymes is the current focus of the Quinn Research Group. Prominent among the cholinesterases are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which function in the nervous systems of animals, including humans (1). AChE plays an important role in the central nervous system, where it functions along with acetycholine receptors in excitatory neurotransmission. AChE possesses very high catalytic efficiency, and a continuing goal is to understand the structural and mechanistic bases of the high catalytic power of the enzyme. This understanding in turn informs the design of ultrapotent AChE inhibitors, such as the trifluoroketone shown in the accompanying picture (2, 3). The trifluoroketone is covalently bound to the serine nucleophile of the active site at the bottom of a deep gorge, and a second binding site where ligands first interact is situated ~ 20 Å away at the enzyme’s surface. AChE is the therapeutic target of FDA approved drugs for the treatment of the cognitive deficit associated with Alzheimer’s disease. These drugs bind in the active site of the enzyme in modes that overlap the binding loci of the trifluoroketone in the picture. A second goal is to use the trifluoroketone pharmacophore in the synthesis of more elaborate AChE inhibitors that are expected to span from the active site to the binding site at the enzyme’s surface. It is hoped that such multifunctional inhibitors will not only alleviate the cognitive deficit caused by but will also slow the progression of Alzheimer’s disease. BuChE may also function in cholinergic neurotransmission in the central nervous system, though its role is not as well defined as that of AChE. Work on both cholinesterases uses various experimental approaches, which include enzyme kinetics, isotope effects (4), investigations of mutant enzymes (3, 4), and organic synthesis of substrate analogs and enzyme inhibitors.

Date Last Modified: 06/07/2014 - 21:56:23