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dc.contributor.advisorWilliams, Dwight A.
dc.contributor.authorJohnson, Luke Norman
dc.descriptionviii, 22 p.en_US
dc.description.abstractThe endocannabinoid system is comprised of two known subtypes, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). The high sequence homology of CB1 and CB2 has limited the number of ligands that demonstrate selectivity for CB1 over CB2 or vice versa. Ligands targeted to the CB1 receptor have shown therapeutic potential towards a broad range of diseases including sleep disorders, diarrhea, neurodegenerative diseases, migraines, and seizures. As such it would be beneficial to develop CB1 selective ligands as potential therapeutics. The naturally occurring kavalactone yangonin has shown moderate binding affinity for CB1 however the functional activity of yangonin at CB1 is unknown nor its CB1/CB2 selectivity. Given this it would be beneficial to use computational methods such as ligand docking and molecular dynamics to provide more information about the protein-ligand interactions between CB1 and Yangonin. The work presented in this study highlights our initial ligand docking studies to identify an optimal binding pose within the binding pocket of CB1 and molecular dynamics simulations to understand protein-ligand interactions. Key results from this work showed that Yangonin may interact mainly with hydrophobic residues Phe102, Met103, Ile105, Gly166, Phe170, Phe379, Cys386, and Leu387 and forms a hydrogen bond with Ser383. These results have been applied to design a series of novel Yangonin analogues with potentially greater selectivity and affinity for CB1. Their chemical synthesis is also presented herein.en_US
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Chemistry Senior Individualized Projects Collection
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.
dc.titleComputational Study and Subsequent Synthesis of Kavalactones as Potential CB1 Ligandsen_US

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  • Chemistry Senior Individualized Projects [860]
    This collection includes Senior Individualized Projects (SIP's) completed in the Chemistry Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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