Date of Award
Doctor of Philosophy (PhD)
This thesis focuses on the design and/or conjugation of peptide-based drugs [oxytocin (OT) or glucagon-like peptide 1 (GLP-1)] for the treatment of type 2 diabetes mellitus and/or obesity with the intent of mitigating common negative side effects caused by their activity in the human hindbrain. Preventing blood brain barrier (BBB) penetrance was achieved through a process termed ‘corrination’: the conjugate modification of a compound, peptide, or protein with a corrin ring containing compound such as vitamin B12 (B12) or biosynthetic derivatives, thereof. Corrination was also used to increase solubility and/or decrease aggregation of peptides with such draw backs in terms of clinical translation. This thesis will also describe a set of new peptides that combine both human GLP-1 and α-Latrotoxin, the latter found in the venom of the black widow spider, sharing amino acid sequence similarity with human GLP-1.
Liles, Amber, "Design, synthesis, and bioconjugation of novel peptide-based drugs to mitigate negative hindbrain side effects for the treatment of type 2 diabetes and obesity" (2023). Dissertations - ALL. 1676.
Available for download on Wednesday, June 12, 2024