Exploration of Multivalency In Noncovalent Coiled-Coil Coupled Covalent Exchange & Development of Sensor Arrays Utilizing a Systems Based Approach

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  • Carpenter, Benjamin Allen
    • College of Arts and Sciences, Department of Chemistry
Abstract
  • Chemistry originated as the study and characterization of compounds in relative isolation. With the advent of supramolecular chemistry, researchers began to explore the ways in which molecules can interact with one another. Now that supramolecular chemistry has been well established, scientists have begun to investigate large networks of interacting molecules as the next step of building complexity. This approach gave rise to the newly minted field of systems chemistry. These networks of interacting molecules have exhibited interesting properties, known as emergent properties, that are not observed by the individual pieces. These properties often mimic behaviors observed in the complex biological environments that allow for life. In this dissertation, two projects will be discussed that utilized a dynamic combinatorial chemistry (DCC) approach to study two different systems. The first study presented herein utilizes a DCC library that combines dynamic covalent exchange (disulfide exchange) with dynamic noncovalent interactions (coiled-coils). These studies show that there is a cooperative interplay between the thermodynamic effects of both the covalent and noncovalent domains that results in behaviors not observed in each domain individually. Firstly, coiled-coil interactions that are too weak to form as lone peptide strands but can fold when covalently tethered via a monomer, and his is due to a decrease in effective concentration. In addition, the amount of potential energy stored in the peptide sequence can be calculated using the ratio of helicity when tethered to the helicity when not tethered (the helical improvement). The coiled-coils are able to drive higher order oligomerization in the library to compensate for non-ideal pairings in the library. This occurs due to a multivalent effect that results from the noncovalent network that forms in these oligomers. The second project described herein uses a multi-library approach to developing a sensor array. The complexity provided from multiple libraries, built from the same set of starting monomers, provides an opportunity to do a high throughput screen of conditions for the development of numerous sensor arrays. This work has shown versatility in how these sensor arrays can function, and a reductive analysis approach has been developed to make data workup more efficient.
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  • In Copyright - Educational Use Permitted
Advisor
  • Waters, Marcey
  • Waters, Marcey
  • Johnson, Jeffrey
  • Knight, Abigail
  • Leibfarth, Frank
  • Gagne, Michel
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2021
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