ProfessorDirector, Center for Drug Discovery
Office: 116 Mugar Hall
Ph.D., Medicinal Chemistry, University of Kansas Post-Doctoral Fellow, University of California, Berkeley, CA
Drug Design Synthesis; Molecular Recognition; Membrane Biophysics; Membrane Protein Purification and Characterization; Nuclear Magnetic Resonance Spectroscopy; High Troughput Technology
Major Research Areas
The Endocannabinoid System in Drug Discovery: Cannabinergic drugs modulate the central nervous and immune systems by acting through two receptors (CB1; CB2) and two classes of endogenous ligands represented by anandamide and 2-arachidonyl glycerol (endocannabinoids). The endocannabinoid system is further regulated by the inactivating enzyme, fatty acid amide hydrolase (FAAH), and a newly discovered transport system. We are studying the interactions of cannabinergic ligands with the above receptors, enzymes and transporters using a combination of chemical, biochemical, biophysical and computational methods. Our results are further used to design and synthesize novel therapeutically useful drugs for pain, appetite and central nervous system diseases.
Interactions of Drugs with Membranes: We study the effects of drug molecules on membranes using solution and solid-state nuclear magnetic resonance and computational methods and use the results are used to design and synthesize improved medications. The classes of drugs being studied include cannabinoids, steroids and antineoplastic ether lipids. The work also includes studying the mechanism by which these molecules are transported across the blood brain barrier.
Our research is well supported by NIH grants and offers opportunities for training in model medicinal chemistry. Choices of projects within the Center for Drug Discovery include: a) drug design and synthesis; b) chemical/biochemical approaches for studying drug:receptor interactions and; c) the role of membranes in drug action using biophysical methods.
J. Guo, S. Pavlopoulos, X. Tian, D. Lu, S. Nikas, S. Nikas, D. Yang and A. Makriyannis, “Conformational Study of Lipophilic Ligands in Phospholipid Model Membrane Systems By Solution NMR.” J. Med. Chem., 46, 4838-4846 (2003).
M. M. Ibrahim, H. Deng, A. Zvonok, D. Cockayne, J.Kwan, H. P. Mata, T. W. Vanderah, J. Lai, F. Porreca, A. Makriyannis and T. P. Malan, “Activation of CB2 Cannabinoid Receptors By AM1241 Inhibits Experimental Neuropathic Pain: Pain Inhibition By Receptors Not Present In CNS.” Proc. Natl. Acad. Sci., 100, 10529-10533 (2003).
Makriyannis, A. and A. Goutopoulos, “Cannabinergics: Old and New Therapeutic Possibilities.” Makriyannis, A. and D. Biegel (Eds.), Drug Discovery Strategies and Methods. 1. 89-128, Marcel Dekker, Inc., New York, NY (2003).