Lessons learned from studying peptide chemistry and the development in mimicking its modularity in the design of a new oligomer using guanidiniums, alpha-diketones, and boronic acids

Peptide chemistry is a versatile tool in the development of diverse compounds that can be applied in various contexts: biology, drug development, organic synthesis, chemo sensing, combinatorial library design, and unnatural foldamer formation. This chemistry is highly optimized that commercial instruments are available for the fast production of these compounds. Despite the optimization, there are new, engaging avenues scientists can still explore in this well-established field. Our work in the Anslyn group is currently focused to incorporate more functionality into peptides beyond the repertoire given by nature. These efforts are targeted for many uses as described in this dissertation. The lessons learned from synthetic peptide design have directed our group also to explore the development of new oligomer systems that take a modular approach in its elongation as used in peptide chemistry. The use of synthetically accessible monomers that are linked by a reliable reaction is the simple, but powerful guiding principle behind the work presented here. Chapter 2 describes the development of a methodology to modify peptides in a sequential and selective manner targeting the most reactive amino acids. The chemistry presented in this chapter serves as the basis for the synthesis of model peptides with fluorescent probes. In chapter 3, these fluorescently labeled peptides are used for proof-of-concept studies for a new single-molecule protein-sequencing platform. Inspiration taken from chapters 2 and 3 brings chemistries facilitating the introduction of ortho- (aminomethyl)boronic acids into peptides. Chapter 5 explores chemical modifications ligands allowing for induced higher-order structuring. Finally, Chapter 6 leaves the peptide space to explore a supramolecular oligomer that will serve as the foundation for a new backbone branched with side chain functionalities.