{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Drug discovery through combination of computational screening and design, chemical synthesis and biological evaluations","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/77087"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"A long-standing problem with the use of conventional cancer chemotherapy is the inherent lack of tumor specificity.  Tumor-targeting drug-delivery systems (TTDS) have since been explored to overcome this deficiency.  These drug conjugates can deliver potent cytotoxic drugs specifically to tumors and tumor cells with minimal systemic toxicity.  Among various tumor-targeting molecules discussed, Designed Ankyrin Repeat Proteins (DARPins) represent a new approach to tumor targeting.  In particular, DARPins targeting CD326 Epithelial Cell Adhesion Molecule (EpCAM) receptors provide an effective cancer target, as EpCAM is critical to the regulation of cellular matrix composition and overall cancer aggressiveness. Botulism is a human illness caused by the bacterium Clostridium botulinum which results in fatal flaccid paralysis and eventual respiratory failure.  Clostridium botulinum produces botulinum neurotoxins (BotNTs), which by themselves are considered by the CDC to be potential Category A bioterrorism weapons.  The light chain protease domain of BotNTs efficiently cleaves SNARE proteins which in turn regulates neurotransmitter release in motor neurons, resulting in the inhibition of neuronal transmission.  Discussed is the use of a novel footprint-based virtual screening to identify compounds with inhibitory activity against BotNTA-LC catalytic activity. Fatty acid binding proteins (FABPs), have recently been identified as intracellular transporters for the endocannabinoid anadamide (AEA).  Furthermore, animal studies by others have shown that elevated levels of endocannabinoids result in beneficial pharmacological effects on stress, pain and inflammation and also ameliorate the effects of drug withdrawal.  Accordingly a novel α -truxillic acid derivative (SB-FI-26) was synthesized and assayed for its inhibitory activity against FABP5.  Additionally, we found SB-FI-26 to act as a potent anti-nociceptive agent with mild anti-inflammatory activity in mice, which strongly supports our hypothesis that the inhibition of FABPs and subsequent elevation of anandamide is a promising new approach in drug discovery."},{"label":"dcterms.available","value":"2017-09-20T16:51:56Z"},{"label":"dcterms.contributor","value":"Simmerling, Carlos"},{"label":"dcterms.creator","value":"Berger, William Theodore"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:51:56Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:51:56Z"},{"label":"dcterms.description","value":"Department of Chemistry."},{"label":"dcterms.extent","value":"349 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/77087"},{"label":"dcterms.issued","value":"2013-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:51:56Z (GMT). No. of bitstreams: 1\nBerger_grad.sunysb_0771E_11645.pdf: 22062420 bytes, checksum: f2d9f3e3cbf139bee9ebc0b491002cb8 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Berger W. T., Botulism, FABP, Medicinal Chemistry, SB-FI-26, SB-T-1214"},{"label":"dcterms.title","value":"Drug discovery through combination of computational screening and design, chemical synthesis and biological evaluations"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/96%2F02%2F67%2F96026723936692131029169741139832625400/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/96%2F02%2F67%2F96026723936692131029169741139832625400","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}