Novel Ligands for GPCRs

This is a collaborative project where new ligands for GPCRs are designed and optimized using the molecular modeling of the group of Dr. Patricia Reggio at UNCG. Targeted libraries of compounds are then synthesized in my group. The syntheses are designed to be convergent so that a large number of analogs can be synthesized in a minimal number of steps. The compounds are then sent to Temple University where the groupof Dr. Mary Abood determines their ability to agonize or antagonize the different GPCRs. This information is then used to modify the modeling data which enables the iterative optimization cycle to continue. Funding for this project has been provided by the National Institute of Health in the form of R01 (DA023204) and an R21 (NS077347) grants. This support is gratefully acknowledged.

Selected Publications:

“Identification of the GPR55 Antagonist Binding Site Using a Novel Set of High-Potency GPR55 Selective Ligands”
Evangelia Kotsikorou, Haleli Sharir, Derek M Shore, Dow P. Hurst, Diane L. Lynch, Karla E. Madrigal, Susanne Heynen-Genel, Loribelle B. Milan, Thomas D.Y. Chung, Herbert H. Seltzman, Yushi Bai, Marc G. Caron, Lawrence S. Barak, Mitchell P Croatt, Mary E Abood, and Patricia H. Reggio
Biochemistry 201352, 9456-9469.

“Design, Synthesis, and Analysis of Antagonists of GPR55:  Piperidine-Substituted 1,3,4-oxadiazol-2-ones”
Maria Elena Meza-Avina, Mary A. Lingerfelt, Linda Console-Bram, Thomas F. Gamage, Haleli Sharir, Kristen E. Gettys, Dow P. Hurst, Evangelia Kotsikorou, Derek M Shore, Marc G. Caron, Narasinga Rao, Larry S. Barak, Mary E Abood, Patricia H. Reggio, and Mitchell P Croatt
Bioorganic & Medicinal Chemistry Letters 201626, 1827-1830.
“Structure-Activity Relationships of Benzothiazole GPR35 Antagonists
Manahil M. Abdalhameed, Pingwei Zhao, Dow P. Hurst, Patricia H. Reggio, Mary E Abood, and Mitchell P Croatt
Bioorganic & Medicinal Chemistry Letters 201727, 612-615.

“Design, synthesis and biological evaluation of GPR55 agonists”
Lara Fakhouri, Christopher D. Cook, Mohammed H. Al-Huniti, Linda M. Console-Bram, Dow P. Hurst, Michael B.S. Spano, Daniel J. Nasrallah, Marc G. Caron, Larry S. Barak, Patricia H. Reggio, Mary E. Abood, Mitchell P. Croatt
Bioorganic & Medicinal Chemistry 201725, 4355-4367.