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DEVELOPMENT AND EVALUATION OF REVERSE-ENGINEERED MULTIVALENT LIGANDS FOR CANCER IMAGING AND THERAPYHandl, Heather Lyn January 2005 (has links)
Multimeric ligands have the potential to be developed as targeted imaging agents and therapeutics for the diagnosis and treatment of cancer. Multimeric ligands consist of multiple binding residues tethered together by a linker and are capable of simultaneous binding to multiple receptors. This dissertation details the proof-of-principle experiments that establish that multimeric ligands bind with an increased affinity and cooperativity compared to their monomeric counterparts. We have chosen to evaluate combinations of ligands for the human melanocortin 4 receptor (hMC4R), human delta-opioid receptor (hdOR), cholecystokinin-B receptor (CCK-BR), and oxytocin receptor (OTR).Multivalent ligands can be homomeric, meaning that all ligands bind to the same receptor type, or they may be heteromeric, meaning that they bind to different types of receptors. We have evaluated homodimer and homotrimer binding to hMC4Rs, and heterodimer binding to hMC4Rs and hdORs. Ligands for the receptors were tethered together using backbones constructed of polyethylene glycol (PEG) units or different combinations of amino acid repeats. The effects of linker length and rigidity on the binding of multivalent ligands have been evaluated. Additionally, this dissertation details the development of a new lanthanide based binding method used to monitor receptor-ligand interactions. This assay makes use of lanthanide labels attached to a peptide that binds specifically to the receptor of interest. The amount of bound ligand is detected using time-resolved fluorescence (TRF). This assay produces results which are highly reproducible, require less setup time and reagents and do not require special waste disposal, all advantages over the traditional radioligand binding assays. This lanthanide based binding assay has been adapted to evaluate ligand binding to the hMC4R and hdOR.
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Nutritional modulation of the insulin-like growth factor (IGF) system of the dog and catMaxwell, Amanda January 2000 (has links)
No description available.
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Protein-ligand interactions for the OppA systemDavies, Thomas Glanmor January 2000 (has links)
No description available.
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Biochemical and structural studies of the CysB protein from Klebsiella aerogenesTyrrell, Richard January 1995 (has links)
No description available.
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Structural studies of penicillin acylaseDone, Sarah Helen January 1996 (has links)
No description available.
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Cloning and knock-out of the mouse gene coding for the high mobility group 2 protein (HMG2)Ronfani, Lorenza January 2000 (has links)
No description available.
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The development of immunoassays for follistatin and activin and their clinical applicationsEvans, Lee W. January 1997 (has links)
No description available.
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Comparative effects of AT and GC sequence selective DNA minor groove binding agentsForrow, Stephen Michael January 1995 (has links)
No description available.
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Functional analysis of a homeobox-containing gene expressed during early Xenopus developmentTrindade, Margarida January 2000 (has links)
No description available.
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The control of cell motility and differentiation by Ras pathwaysTuxworth, Richard Ian January 1999 (has links)
No description available.
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