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Synthesis Of Ag10 Analogs And Optimization Of Ttr Ligands For Half-Life Enhancement (Tlhe) Of Peptides, Raghavendra Jampala

University of the Pacific Theses and Dissertations

The misassembly of soluble proteins into toxic aggregates, including amyloid fibrils, underlies a large number of human degenerative diseases. Cardiac amyloidosis, which is most commonly, caused by aggregation of Immunoglobulin (Ig) light chains or transthyretin (TTR) in the cardiac muscle, represent an important and often underdiagnosed cause of heart failure. TTR-mediated amyloid cardiomyopathies are chronic and progressive conditions that lead to arrhythmias, biventricular heart failure, and death. As no Food and Drug Administration-approved drugs are currently available for treatment of these diseases, the development of therapeutic agents that prevent TTR-mediated cardiotoxicity is desired. AG10 is a potent and selective kinetic …