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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
Jennifer Stockdill
Abstract
The interest in bioactive peptides as therapeutic agents has increased over the years due to their large surface area, site-selectivity and synthetic accessibility. Although chemical synthesis has enabled access to a wide range of peptides, there are limitations that result from 9-Fluorenylmethyloxycarbonyl (Fmoc) Solid-Phase Peptide Synthesis (SPPS). Aspartimide formation and subsequent by-products are a result from unfavorable aspartic acid positioning in peptide synthesis due to repetive base exposure. The directionality of peptide assembly implemented in Fmoc SPPS is limited to the C to N direction due to traditional carboxylic acid activation strategy generating epimerized products. Recently, NAUs were described to be successufly displaced to access Cterminally modified peptides and macrocycles while maintaining the stereointegry of the C-terminal amino acid establishing NAUs as the mildest activing agent in peptide chemistry. This thesis describes the application of the the mild activating properties of NAU to deter aspartimide formation and promote the N to C assemble of peptide on resin. Also, the development of an N-to-C platform which entails amino acid building blocks, Nterminal linker strategy, conditions for epimerization free N-to-C SPPS, and NAU promoted bidirecitonal synthesis will be discussed.
Recommended Citation
Mendoza, Lawrence, "N-Acyl Urea Activation Of Carboxylic Acids As An Enabling Strategy For Peptide Synthesis" (2023). Wayne State University Dissertations. 3834.
https://digitalcommons.wayne.edu/oa_dissertations/3834