Structure-Guided Design and Synthesis of Small Molecules Targeting Hepatitis C Virus Internal Ribosome Entry Site RNA | Posted on:2015-09-23 | Degree:Ph.D | Type:Thesis | University:University of California, San Diego | Candidate:Ding, Kejia | Full Text:PDF | GTID:2474390017498055 | Subject:Chemistry | Abstract/Summary: | | This study focuses on the structure-guided design and synthesis of small molecules that target hepatitis C virus internal ribosome entry site subdomain IIa RNA - a structural element that plays a key role in the viral protein translation initiation process. A series of aryl-substituted benzimidazole molecules was designed using guidance from a shape-similarity screening that utilized the structure of a known subdomain IIa RNA-binding benzimidazole translation inhibitor as the query molecule. The syntheses of the designed aryl-substituted benzimidazole molecules were described. Their binding affinities towards the target RNA were assessed by a FRET assay. The structure-binding relationship of these molecules was analyzed. The second part of the study explores the design and synthetic development of 2-aminoquinazolin-4-one and 2-amino-lin-benzoguanine molecules, whose design were guided by the ligand-bound subdomain IIa RNA crystal structure. | Keywords/Search Tags: | Molecules, Virus internal ribosome, Structure-guided design and synthesis, Subdomain iia RNA | | Related items |
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