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Sommayah Sayed

Posted on March 30, 2016


Date - March 30, 2016
1:00 pm


MS Thesis – 602


GPR55, is a G-protein coupled receptor (GPCR), that was first discovered in 1990 and deorphanized in 2006.[1] The homology model of the receptor in the active and inactive state is based off of the β – adrenergic receptor. A potent agonist of GPR55 is the endogenous LPI and one antagonist is ML192.[2]   Due to the biological diseases associated with GPR55 a more potent antagonist or agonist is needed that can deactivate or activate the receptor in order to further elucidate the role and function of GPR55 in the body.[3]  The focus of the research presented is to synthesize a variety of analogs of GPR55 with the goal of finding a more potent antagonist then ML192. The analogs that synthesized were subjected to biological assay testing and computational analysis.   Five different novel analogues were synthesized that further probed the role of one section of the molecule and acquire some structure-activity relationships.

[1] Elbegdorj, O.; Westkaemper, R.B.; Zhang, Y. “A homology modeling study toward the understanding of three-dimensional structure and putative pharmacological profile of the G-protein coupled receptor GPR55” Journal of Molecular Graphics and Modeling 2013.

[2] Kotsikorou, E.; Sharir, H.; Shore, D.M.; Hurst, D.P.; Lynch, D.L.; Madrigal, K.E.; Heynen-Genel, S.; Milan, L.B.; Chung, T.D.Y; Seltzman, H.H.; Bai, Y.; Caron, M.G.; Barak, L.S.; Croatt, M.P.; Abood, M.E.; Reggio, P.H. “Identification of the GPR55 Antagonist Binding Site using a Novel Set of High-Potency GPR55 Selective Ligands” Biochemistry 2013, 52, 9456-9469.

[3] Henstridge, C.M.; Balenga, N.A.; Kargl, J.; Andradas, C.; Brown, A.J.; Irving, A.; Sanchez, C.; Waldhoer, M. “Minireview: Recent Developments in the Physiology and Pathology of the Lysophosphatidylinositol- Sensitive Receptor GPR55” Molecular Endocrinology 2011, 25, 1835-1848.